83 results on '"Ching-Fai Kwok"'
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2. Exercise reduces body fat and improves insulin sensitivity and pancreatic β-cell function in overweight and obese male Taiwanese adolescents
- Author
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Kuang-Chung Shih and Ching-Fai Kwok
- Subjects
β-cell function ,Exercise ,Insulin resistance ,Obesity ,Type 2 diabetes ,Pediatrics ,RJ1-570 - Abstract
Abstract Background Improvements in insulin resistance and pancreatic β-cell function have been shown following exercise in adults with obesity; however, few adolescent-based studies have been conducted. This study examined the impact of exercise training on body fat and insulin sensitivity and secretion in overweight and obese adolescents. Methods The effects of a 12-week exercise program on the parameters of adiposity and glucose homeostasis were investigated in 47 overweight and obese male adolescents. Results After the exercise training program, body weight, body mass index, waist circumference, and body fat were significantly decreased (P
- Published
- 2018
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3. A Single Center, Open-Labeled Trial To Investigate The Pharmacokinetics of Insulin Detemir in Healthy Taiwanese Subjects
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Low-Tone Ho and Ching Fai Kwok
- Subjects
Pharmacokinetics ,business.industry ,medicine ,Pharmacology ,Single Center ,business ,Insulin detemir ,medicine.drug - Abstract
Backgrounds: Insulin detemir(nn304) is a long-acting insulin analogue reported to provide more predictable blood glucose level throughout the day, leading to a lower within-subject variability compared to NPH insulin. Pharmacokinetic profiles of insulin detemir had not been investigated in Taiwanese. This study was to determine whether there is a differencebetween Taiwanese subjects in pharmacokinetic profile of insulin detemir compared to Caucasian subjects.Methods: Pharmacokinetic profile of insulin detemir was measured in twenty male Taiwaneses(nn304-3023). Eligible subjects were given insulin detemir as a single dose subcutaneous injection at 0.5 U/kg body weight in the mid-thigh using NovoPen® 3 device. 32-hour serum insulin detemir concentrations were measured. Hypoglycemia and adverse events were recorded. The results were compared to data obtained from a previous trial inCaucasian subjects (nn304-1451).Results: There was no significant difference between Taiwanese (nn304-3023) and Caucasian(nn304-1451) in the primary endpoint, AUC(0–∝), and the secondary endpoints, AUC(0–24h), and t1/2. However, the secondary endpoints, Cmax was 40% higher, tmax was shorter(270.0 vs. 420.0 min) and AUC(0–5h) was 2-fold more in Taiwanese. When only male subjects were included in the comparator trial (nn304-1451), the t1/2 was significantly shorter in Taiwanese(348 min vs 404 min). There was no significant difference in the mean blood glucose concentrations between Taiwanese and Caucasian subjects. A single episode of hypoglycemia(53 mg/dL) was reported in a 24-year-old male approximately 2.5 hours after the administration of insulin detemir. He was able to treat himself for the episode.Conclusion: In this pharmacokinetic evaluation of a single dose administration of insulin detemir in Taiwanese male subjects, the AUC(0–∝), and AUC(0–24h) were not different from that of Caucasians in the comparator trial. However, insulin detemir appeared to be more rapidly absorbed in Taiwanese males. Further studies are warranted to elucidate its pharmacodynamic response and mechanisms. Finally, there was no clinically relevant safety concern raised in this study. (Funded by research grant from Novo Nordisk, Taiwan; first registration date 22/12/2011 ClinicalTrials.gov number, NCT01497587.
- Published
- 2021
4. Endothelin-1 induces lipolysis through activation of the GC/cGMP/Ca
- Author
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Chih-Chan, Lien, Wei-Hsian, Yin, De-Ming, Yang, Luen-Kui, Chen, Chien-Wei, Chen, Shui-Yu, Liu, Ching-Fai, Kwok, Low-Tone, Ho, and Chi-Chang, Juan
- Subjects
Lipolysis - Abstract
Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced and secreted mainly by endothelial cells. Recent studies indicate that ET-1 can regulate lipid metabolism, which may increase the risk of insulin resistance. Our previous studies revealed that ET-1 induced lipolysis in adipocytes, but the underlying mechanisms were unclear. 3T3-L1 adipocytes were used to investigate the effect of ET-1 on lipolysis and the underlying mechanisms. Glycerol levels in the incubation medium and hormone-sensitive lipase (HSL) phosphorylation were used as indices for lipolysis. ET-1 significantly increased HSL phosphorylation and lipolysis, which were completely inhibited by ERK inhibitor (PD98059) and guanylyl cyclase (GC) inhibitor (LY83583). LY83583 reduced ET-1-induced ERK phosphorylation. A Ca
- Published
- 2021
5. Visfatin Promotes Monocyte Adhesion by Upregulating ICAM-1 and VCAM-1 Expression in Endothelial Cells via Activation of p38-PI3K-Akt Signaling and Subsequent ROS Production and IKK/NF-кB Activation
- Author
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Low-Tone Ho, Tse Ting Kuan, Chi Chang Juan, Ching Fai Kwok, Wei Chih Huang, Ting Chia Hsu, Shao Yun Wu, Luen Kui Chen, Yu Ting Lin, and Deng Yuan Jian
- Subjects
0301 basic medicine ,Physiology ,Vascular Cell Adhesion Molecule-1 ,IκB kinase ,p38 Mitogen-Activated Protein Kinases ,Monocytes ,lcsh:Physiology ,lcsh:Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Downregulation and upregulation ,Cell Adhesion ,Humans ,lcsh:QD415-436 ,VCAM-1 ,Phosphorylation ,Cell adhesion ,Nicotinamide Phosphoribosyltransferase ,Protein kinase B ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,Phosphoinositide-3 Kinase Inhibitors ,Mitogen-Activated Protein Kinase 1 ,ICAM-1 ,Mitogen-Activated Protein Kinase 3 ,lcsh:QP1-981 ,Chemistry ,NF-kappa B ,Endothelial Cells ,NADPH Oxidases ,Intercellular Adhesion Molecule-1 ,Cell biology ,Up-Regulation ,Endothelial stem cell ,030104 developmental biology ,030220 oncology & carcinogenesis ,I-kappa B Proteins ,Reactive Oxygen Species ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Background/aims Visfatin is known to act as a mediator in several metabolic disorders, such as obesity, diabetes, and cardiovascular diseases. This study aimed to investigate the effect of visfatin on the adhesion of THP-1 monocytes to human vascular endothelial cells and the underlying mechanism. Methods Monocytes adhesion to endothelial cells was determined by using fluorescence-labeled monocytes. ICAM-1 and VCAM-1 expression in endothelial cells were measured by western blotting. Production of reactive oxygen species (ROS) was measured by using a fluorescent dye. The amounts of nuclear factor-kappa B (NF-κB) and phosphorylation of inhibitory factor of NF-κB (IκB) were determined by using western blot analysis. The translocation of NF-κB from the cytoplasm to the nucleus was determined by using immunofluorescence. Results Here we showed that visfatin significantly caused the upregulation of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells, as well as enhanced monocyte adhesion to endothelial cells. Moreover, we found that inhibition of PI3K, Akt, and p38 MAPK activation significantly prevented visfatin-enhanced expression of ICAM-1 and VCAM-1 and monocyte adhesion to endothelial cells. Visfatin enhanced ROS production and IKK/NF-кB activation and then led to upregulation of ICAM-1 and VCAM-1 and enhanced monocyte adhesion to endothelial cells. These effects were also p38/PI3K/Akt-dependent. Conclusion These results demonstrated that visfatin promoted monocyte-endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression via the activation of p38/PI3K/Akt signaling and downstream ROS production and IKK/NF-кB activation.
- Published
- 2019
6. Endothelin-1 induces lipolysis through activation of the GC/cGMP/Ca2+/ERK/CaMKIII pathway in 3T3-L1 adipocytes
- Author
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Ching-Fai Kwok, Chih-Chan Lien, Wei-Hsian Yin, Chi Chang Juan, De Ming Yang, Shui-Yu Liu, Luen-Kui Chen, Chien-Wei Chen, and Low-Tone Ho
- Subjects
MAPK/ERK pathway ,Chemistry ,Extracellular ,Lipolysis ,Phosphorylation ,3T3-L1 ,Cell Biology ,Signal transduction ,Inositol trisphosphate receptor ,Molecular Biology ,Endothelin 1 ,Cell biology - Abstract
Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced and secreted mainly by endothelial cells. Recent studies indicate that ET-1 can regulate lipid metabolism, which may increase the risk of insulin resistance. Our previous studies revealed that ET-1 induced lipolysis in adipocytes, but the underlying mechanisms were unclear. 3T3-L1 adipocytes were used to investigate the effect of ET-1 on lipolysis and the underlying mechanisms. Glycerol levels in the incubation medium and hormone-sensitive lipase (HSL) phosphorylation were used as indices for lipolysis. ET-1 significantly increased HSL phosphorylation and lipolysis, which were completely inhibited by ERK inhibitor (PD98059) and guanylyl cyclase (GC) inhibitor (LY83583). LY83583 reduced ET-1-induced ERK phosphorylation. A Ca2+-free medium and PLC inhibitor caused significant decreases in ET-1-induced lipolysis as well as ERK and HSL phosphorylation, and IP3 receptor activator (D-IP3) increased lipolysis. ET-1 increased cGMP production, which was not affected by depletion of extracellular Ca2+. On the other hand, LY83583 diminished the ET-1-induced Ca2+ influx. Transient receptor potential vanilloid-1 (TRPV-1) antagonist and shRNA partially inhibited ET-1-induced lipolysis. ET-1-induced lipolysis was completely suppressed by CaMKIII inhibitor (NH-125). These results indicate that ET-1 stimulates extracellular Ca2+ entry and activates the intracellular PLC/IP3/Ca2+ pathway through a cGMP-dependent pathway. The increased cytosolic Ca2+ that results from ET-1 treatment stimulates ERK and HSL phosphorylation, which subsequently induces lipolysis. ET-1 induces HSL phosphorylation and lipolysis via the GC/cGMP/Ca2+/ERK/CaMKIII signaling pathway in 3T3-L1 adipocytes.
- Published
- 2022
7. MON-459 Bilateral Killian-Jamieson Diverticulum Mimicking Thyroid Nodules
- Author
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Yu-Yi Lin, Harn-Shen Chen, Ching-Fai Kwok, and Hsin-Kai Wang
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Thyroid nodules ,Thyroid ,Killian–Jamieson diverticulum ,business.industry ,Endocrinology, Diabetes and Metabolism ,Thyroid Disorders Case Reports III ,medicine ,Anatomy ,medicine.disease ,business ,AcademicSubjects/MED00250 - Abstract
Background In recent years, incidence and prevalence of thyroid and extrathyroid lesion is increasing in the worldwide due to increase awareness of medical check-up, and widespread use of imaging techniques. A Killian Jamieson diverticulum (KJD), a rare type of hypopharyngeal pulsion diverticulum outpouching from the lateral wall of the proximal cervical esophagus, was incidentally detected and likely to be misinterpreted as a thyroid nodule while performing thyroid sonography. Clearly differentiate between those lesions is essential to avoid unnecessary invasive procedure. Here we report a typical case of bilateral Killian Jamieson diverticulum mimicking thyroid nodules. Clinical case A 57-year-old Taiwanese man was referred to our endocrine outpatient department for further evaluation of thyroid nodules. The lesions were discovered while sonographic examination performed in the clinic for routine medical check-up. He denied having dysphagia, epigastric pain, odynophagia, halitosis, chronic cough or acid regurgitation, body weight loss, fever and dyspnea. He had no previous systemic disease and no prior radiation therapy. He lives in Nangang District, Taipei city. His body weight was 70 kg and BMI was 25. An examination of head and neck was unremarkable. Laboratory data revealed normal thyroid function (TSH: 0.67 uIU/ml; range 0.4~4.0, free T4: 0.83 ng/dl; range 0.9~1.8 and aTPO Clinical lessons KJD is usually incidentally detected and misdiagnosed as a thyroid nodule containing punctuate microcalcification foci as found in papillary thyroid carcinoma. To differentiate these nodules, real time sonographic examination is important. Although rare, non-thyroid lesions originating from the esophagus should be considered in the differential diagnosis of the thyroid nodules to avoid unnecessary invasive fine needle aspiration of thyroid gland.
- Published
- 2020
8. The Shipai cohort for cardiovascular metabolic risk factors and outcome study — Design and preliminary results
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Ya Mei Bai, Tzeng Ji Chen, Harn Shen Chen, Tung Ping Tom Su, Shu Chiung Chiang, Ching Fai Kwok, Shinn Jang Hwang, Low-Tone Ho, and Jui Yao Liu
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Research design ,Adult ,Male ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,030212 general & internal medicine ,Obesity ,Young adult ,Response rate (survey) ,Metabolic Syndrome ,lcsh:R5-920 ,business.industry ,Age Factors ,General Medicine ,Middle Aged ,medicine.disease ,Cardiovascular Diseases ,Research Design ,Cohort ,Female ,Metabolic syndrome ,business ,lcsh:Medicine (General) ,Cohort study - Abstract
Background: The aim of this study was to identify genotypic and phenotypic cardiovascular metabolic risk factors, and to establish risk models of diseases, including diabetes mellitus, cardiovascular disease, stroke, kidney dysfunction and psychiatric disorders, in Taiwanese adults. Methods: In 2009, a community-based cohort study was initiated in the Shipai area of the Shilin and Beitou districts in Taipei. Residents were randomly sampled by age (young adults: 35–44 years and middle-aged adults: 45–55 years) and urbanization (rural and urban). Residents who agreed to participate were scheduled to receive examinations (physical and blood) and answer questionnaires. A ten-year follow-up is anticipated. Metabolic syndrome (MetS) was defined based on the Adult Treatment Panel III guidelines, and individuals with only one or two of the five MetS components was identified for prevention target. Results: The response rate of the 9000 invited residents was 10.1%. After screening, 906 participants were enrolled. While 31.0% (281) had no MetS components, 29.1% (264) had only one, and 22.0% (199) had two. MetS with at least three components was diagnosed in 17.9% (162) of the cohort. Concerning gender difference, 25.4% of men and 13.2% of women had MetS (p
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- 2018
9. Diffuse soft tissue emphysema in anorexia nervosa: A case report
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Liang-Yu Lin, Ching-Fai Kwok, Kam-Tsun Tang, Low-Tone Ho, and Hong-Da Lin
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Emphysema, Pulmonary -- Case studies ,Emphysema, Pulmonary -- Causes of ,Anorexia nervosa -- Risk factors ,Anorexia nervosa -- Case studies ,Food/cooking/nutrition ,Psychology and mental health - Abstract
A patient with anorexia nervosa with spontaneous diffuse soft tissue emphysema and bicytopenia, improved gradually and diffuse soft tissue emphysema was completely resolved. This condition seemed benign and required a short period of hospitalization.
- Published
- 2005
10. The Ankle Brachial Index Exhibits Better Association of Cardiovascular Prognosis Than Non–High-Density Lipoprotein Cholesterol in Type 2 Diabetes
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Chia-Huei Chu, Chii-Min Hwu, Hong-Da Lin, Yi-Chun Lin, Ching-Fai Kwok, Justin G.S. Won, Li-Hsin Chang, Liang-Yu Lin, and Harn-Shen Chen
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Male ,Research design ,medicine.medical_specialty ,Diagnostic Techniques, Cardiovascular ,Taiwan ,Renal function ,Type 2 diabetes ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Ankle Brachial Index ,cardiovascular diseases ,030212 general & internal medicine ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Non high density lipoprotein cholesterol ,Type 2 Diabetes Mellitus ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,body regions ,Cholesterol ,medicine.anatomical_structure ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Cardiology ,Female ,lipids (amino acids, peptides, and proteins) ,Ankle ,business ,human activities ,Cardiovascular outcomes - Abstract
The association between ankle brachial index (ABI) and outcomes in diabetic subjects is controversial. The purpose of this study was to evaluate whether the ABI is more strongly associated with cardiovascular outcomes comparing with non-high-density lipoprotein cholesterol (non-HDL-c).A total of 452 type 2 diabetic subjects followed up for a mean of 5.8 years were grouped by ABI (0.9 versus ≥0.9) and non-HDL-c (100mg/dL versus ≥100mg/dL). Primary outcomes were composite events including all-cause mortality, hospitalization for coronary artery disease, stroke, revascularization, amputation and diabetic foot, and the secondary end point was all-cause mortality.Intergroup differences in percentage of men, duration of diabetes, hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, triglycerides and estimated glomerular filtration rate were significant. A total of 64 composite events and 17 deaths were recorded. A higher number of composite events occurred in the group with abnormal ABI but optimal non-HDL-c than in those with suboptimal non-HDL-c but normal ABI (29% versus 11%, P0.05). A similar trend was observed in all-cause mortality (11% versus 1%, P0.05). The ABI was the dominant risk factor for both end points after adjusting other factors (for composite events, hazard ratio = 0.02, 95% CI: 0.00-0.10, P0.001 and for all-cause mortality, hazard ratio = 0.01, 95% CI: 0.00-0.28, P = 0.006).The ABI was more strongly associated with outcomes in diabetes than non-HDL-c. The ABI should be routinely screened in diabetes even without symptom.
- Published
- 2016
11. VISFATIN PROMOTES FOAM CELL FORMATION BY DYSREGULATING CD36, SRA, ABCA1, AND ABCG1 EXPRESSION IN RAW264.7 MACROPHAGES
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Yu Ting Lin, Low-Tone Ho, Chi Chang Juan, Ching Fai Kwok, and Deng Yuan Jian
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CD36 Antigens ,medicine.medical_specialty ,MAP Kinase Signaling System ,CD36 ,Critical Care and Intensive Care Medicine ,Cell Line ,Mice ,Internal medicine ,medicine ,Animals ,Macrophage ,Nicotinamide Phosphoribosyltransferase ,Receptor ,ATP Binding Cassette Transporter, Subfamily G, Member 1 ,Foam cell ,Receptors, Scavenger ,Regulation of gene expression ,biology ,Atherosclerosis ,Endocrinology ,Gene Expression Regulation ,ABCG1 ,Cell culture ,ABCA1 ,Emergency Medicine ,biology.protein ,Cytokines ,ATP Binding Cassette Transporter 1 ,Foam Cells - Abstract
Visfatin is produced in and secreted from adipocytes. Increased circulating visfatin level is observed in obese subjects. Previous studies demonstrated that visfatin was involved in obesity-related cardiovascular diseases.This study aims to explore the regulatory effects of adipokine visfatin on foam cell formation, a key step in the development of atherosclerosis.Effect of visfatin on protein and mRNA expression of scavenger receptor and ATP binding cassette transporter in RAW264.7 macrophages were measured by western blotting and real-time RT-PCR. To confirm the influence of visfatin-regulated scavenger receptor and ATP binding cassette transporter to foam cell formation, the visfatin-caused changes of ox-LDL uptake, cholesterol efflux, and foam cell formation were determined.Visfatin significantly increased the expression of CD36 and scavenger receptor A (SRA), decreased the expression of ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), and had no effect on the expression of SR-B1. Visfatin increased oxidized-LDL (ox-LDL) uptake and decreased cholesterol efflux, which increased foam cell formation. The PI3K inhibitor LY294002 blocked the effect of visfatin on the protein and mRNA expression levels of CD36, SRA, and ABCG1 and ox-LDL uptake and cholesterol efflux. The ERK inhibitor PD98059 also prevented visfatin-induced ABCA1 instability and subsequently decreased cholesterol efflux.Visfatin upregulated CD36 and SRA expression and downregulated ABCA1 and ABCG1 expression, subsequently increased ox-LDL uptake and decreased cholesterol efflux, and finally promoted foam cell formation via the PI3K- and ERK-dependent pathways.
- Published
- 2016
12. Chronic endothelin-1 infusion causes adipocyte hyperplasia in rats
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Deng Yuan Jian, Ching Fai Kwok, Chih Chan Lien, Chi Chang Juan, Jia Ling Jiang, and Low-Tone Ho
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0301 basic medicine ,medicine.medical_specialty ,Nutrition and Dietetics ,Chemistry ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Adipose tissue ,030209 endocrinology & metabolism ,White adipose tissue ,Hyperplasia ,medicine.disease ,Endothelin 1 ,Fat pad ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,Adipogenesis ,Internal medicine ,Adipocyte ,medicine ,Receptor - Abstract
Objective The aim of this study was to investigate the regulatory mechanism of endothelin-1 (ET-1), an endothelium-derived vasoconstrictor, on adipogenesis in vitro and in vivo. Methods 3T3-L1 preadipocytes were used to explore the mechanisms mediating ET-1 actions on preadipocyte proliferation and adipocyte differentiation. To investigate the in vivo effect of ET-1, male Sprague-Dawley rats were infused with ET-1 or saline for 4 weeks via intraperitoneally implanted osmotic pumps, and the fat pad weight and adipocyte size of adipose tissues were measured. Results ET-1 stimulated preadipocyte proliferation and increased the cell number at the mitotic clonal expansion stage of adipocyte differentiation via the endothelin A receptor (ETAR) and activation of the protein kinase C (PKC) pathway. ET-1, via ETAR, inhibited adipocyte differentiation partially through an ERK-dependent pathway. Furthermore, no significant difference in the body weight and fat pad weight was observed in either ET-1- or saline-infused rats. Compared with saline-infused rats, the adipocyte cell number was significantly increased but the adipocyte size was significantly decreased in ET-1-infused rats. Conclusions Chronic ET-1 infusion increased the number of small adipocytes without the change of white adipose tissue mass in rats, which were associated with ET-1-stimulated preadipocyte proliferation, but not ET-1-suppressed adipocyte differentiation.
- Published
- 2016
13. Exercise reduces body fat and improves insulin sensitivity and pancreatic β-cell function in overweight and obese male Taiwanese adolescents
- Author
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Ching-Fai Kwok and Kuang-Chung Shih
- Subjects
Blood Glucose ,Male ,Pediatric Obesity ,medicine.medical_specialty ,Adolescent ,β-cell function ,medicine.medical_treatment ,Taiwan ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Overweight ,Impaired glucose tolerance ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Insulin-Secreting Cells ,Internal medicine ,Diabetes mellitus ,medicine ,Homeostasis ,Humans ,Glucose homeostasis ,Obesity ,Exercise ,Adiposity ,business.industry ,Insulin ,lcsh:RJ1-570 ,lcsh:Pediatrics ,medicine.disease ,Exercise Therapy ,Treatment Outcome ,Endocrinology ,Pediatrics, Perinatology and Child Health ,medicine.symptom ,business ,Body mass index ,Biomarkers ,Research Article - Abstract
Background Improvements in insulin resistance and pancreatic β-cell function have been shown following exercise in adults with obesity; however, few adolescent-based studies have been conducted. This study examined the impact of exercise training on body fat and insulin sensitivity and secretion in overweight and obese adolescents. Methods The effects of a 12-week exercise program on the parameters of adiposity and glucose homeostasis were investigated in 47 overweight and obese male adolescents. Results After the exercise training program, body weight, body mass index, waist circumference, and body fat were significantly decreased (P
- Published
- 2018
14. Effect of Growth Hormone on Dawn Phenomenon in Healthy Adults
- Author
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Szu-Han Chiu, Low-Tone Ho, Ching-Fai Kwok, Yu-Ching Chou, Sheng-Hwu Hsieh, Chii-Min Hwu, and Kuang-Chung Shih
- Subjects
medicine.medical_specialty ,Evening ,business.industry ,Insulin ,medicine.medical_treatment ,Dawn phenomenon ,Octreotide ,medicine.disease ,Growth hormone deficiency ,NEFA ,Endocrinology ,Internal medicine ,medicine ,business ,Morning ,medicine.drug ,Hormone - Abstract
The purpose of this study was to investigate the involvement of growth hormone in the diurnal variation of insulin sensitivity in healthy adults. Afternoon (16:00 hr) or night (23:00 hr) pretreatment with a subcutaneous injection of normal saline, human growth hormone to mimic the normal nocturnal rise in growth hormone, or octreotide to inhibit endogenous growth hormone secretion to create a state of relative nocturnal growth hormone deficiency, was given 16 hours before undergoing the modified insulin suppression test in healthy subjects. The morning and evening experiments were separated by an interval of at least 3 days. Thus, each subject was tested on six separate occasions arranged in a random order. A higher value of the steady-state plasma glucose (SSPG) is indicative of lower insulin sensitivity. Plasma glucose, serum insulin, insulin-like growth factor-1, nonesterified fatty acids (NEFA), and metabolic clearance rate of insulin (MCRI) were measured. In the normal saline and human growth hormone groups, SSPG levels were lower in the morning than in the evening. Evening SSPG levels, MCRI, and NEFA concentrations were higher in the participants treated with normal saline and growth hormone than in the octreotide group. Differences in SSPG levels between the morning and evening values were higher in the participants pretreated with normal saline and growth hormone than in those treated with octreotide. A diurnal variation in insulin sensitivity existed in healthy subjects. These results provided direct evidence that the role of growth hormone in regulating insulin sensitivity might be related to changes in the MCRI and the metabolism of NEFA in healthy subjects.
- Published
- 2015
15. The Combination of the Ankle Brachial Index and Brachial Ankle Pulse Wave Velocity Exhibits a Superior Association with Outcomes in Diabetic Patients
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Tjin Shing Jap, Chia Huei Chu, Justin G.S. Won, Harn Shen Chen, Ching Fai Kwok, Hong Da Lin, Chin Sung Kuo, Kuang Chung Shih, Chii Min Hwu, Liang Yu Lin, and Li Hsin Chang
- Subjects
Male ,medicine.medical_specialty ,Coronary Artery Disease ,Pulse Wave Analysis ,Coronary artery disease ,Peripheral Arterial Disease ,Diabetes mellitus ,Internal medicine ,Outcome Assessment, Health Care ,Internal Medicine ,medicine ,Humans ,Ankle Brachial Index ,cardiovascular diseases ,Stroke ,Aged ,Retrospective Studies ,business.industry ,Hazard ratio ,General Medicine ,Middle Aged ,medicine.disease ,Diabetic foot ,Confidence interval ,Surgery ,Hospitalization ,body regions ,medicine.anatomical_structure ,Blood pressure ,Diabetes Mellitus, Type 2 ,Cardiology ,Female ,Ankle ,business ,Diabetic Angiopathies ,Follow-Up Studies - Abstract
Objective Patients with type 2 diabetes mellitus (T2DM) and peripheral arterial disease are classified as having very high cardiovascular risks. We therefore sought to determine whether assessments of the ankle brachial index (ABI) and brachial ankle pulse wave velocity (baPWV) together exhibited a superior association with the outcomes of T2DM. Methods A retrospective analysis of patients receiving ABI and baPWV during the period 2005-2007 was performed. Patients A total of 452 subjects were enrolled and followed-up for a mean 5.8 years after being grouped according to the ABI (
- Published
- 2014
16. Begin with the Real-world Patients of Non-goal-achieved Hypercholesterolemia in Taiwan through the Ezetimibe/Simvastatin Tablet – The BRAVO Study
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Tao-Yu Lee, Zhih-Cherng Chen, Dee Pei, Ching-Fai Kwok, Miaw-Jene Liou, Jui-Chu Huang, Chi-Min Lin, and Rue-Tsuan Liu
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Adult ,Male ,Simvastatin ,medicine.medical_specialty ,Time Factors ,Hypercholesterolemia ,Taiwan ,Pharmacology ,Ezetimibe ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,National Cholesterol Education Program ,Triglycerides ,Aged ,business.industry ,Anticholesteremic Agents ,Cholesterol, HDL ,Cholesterol, LDL ,General Medicine ,Middle Aged ,Clinical trial ,Drug Combinations ,Tolerability ,Azetidines ,Female ,lipids (amino acids, peptides, and proteins) ,Ezetimibe/simvastatin ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,medicine.drug ,Cohort study - Abstract
To assess the efficacy, safety, and tolerability of a combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia.A prospective, open-label, multi-center, hospital-based cohort study was conducted to evaluate the efficacy, safety, and tolerability of a single tablet combination of ezetimibe/simvastatin for the treatment of hypercholesterolemia. Taiwanese adults without low-density lipoprotein cholesterol (LDL-C) goal achievement, based on the National Cholesterol Education Program Adult Treatment Panel III guidelines, were treated with ezetimibe/simvastatin once daily for 6 weeks. The primary endpoint was the percentage of patients achieving LDL-C treatment goals after 6 weeks of treatment. Secondary endpoints included percentage change from baseline of LDL-C, total cholesterol, high-density lipoprotein cholesterol, and triglyceride. Safety and tolerability were assessed via clinical and laboratory examinations. The clinicaltrial.gov identifier of this study was NCT00654628.In total, 173 patients with a mean age of 57.9 ± 10.4 years were included. Of these, 57.8% were female and the average body mass index was 25.5 ± 3.4 kg/m(2). After 6 weeks of treatment, the great majority of the patients had reached their treatment goals (90.4% for LDL-C; 87% for TC; and 59% for TG). LDL-C levels were significantly reduced from 156.8 ± 30.8 mg/dL at baseline to 75.9 ± 25.4 mg/dL (51.4%, P 0.0001) after only 6 weeks of therapy. Forty-nine adverse events (AEs), including one non-drug related serious AE, were reported. For non-serious AEs, the most common reported AEs during the entire study period were myalgia and upper respiratory infection (both n = 7). Nine patients dropped out of the study, reportedly due to AEs.A single tablet combination of 10 mg ezetimibe and 20 mg simvastatin in Taiwanese patients with hypercholesterolemia provided high LDL-C goal attainment rates and resulted in significant reductions in LDL-C.
- Published
- 2011
17. Endothelin-1 Suppresses Long-Chain Fatty Acid Uptake and Glucose Uptake Via Distinct Mechanisms in 3T3-L1 Adipocytes
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Ching Fai Kwok, Low-Tone Ho, Ying-Hsiu Lai, and Yueh Chien
- Subjects
medicine.medical_specialty ,Time Factors ,Endocrinology, Diabetes and Metabolism ,CD36 ,medicine.medical_treatment ,Glucose uptake ,Down-Regulation ,Medicine (miscellaneous) ,Mice ,chemistry.chemical_compound ,Endocrinology ,Downregulation and upregulation ,3T3-L1 Cells ,Internal medicine ,Adipocytes ,medicine ,Animals ,Insulin ,Lipolysis ,Phosphatidylinositol ,chemistry.chemical_classification ,Nutrition and Dietetics ,Dose-Response Relationship, Drug ,Endothelin-1 ,biology ,Fatty Acids ,Fatty acid ,Biological Transport ,3T3-L1 ,Receptor, Endothelin A ,Glucose ,chemistry ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Insulin Resistance ,Energy Metabolism ,Metabolic Networks and Pathways - Abstract
Endothelin-1 (ET-1) has been demonstrated to induce insulin resistance (IR) and lipolysis, raising the possibility that ET-1 may also contribute to the elevated fatty acid levels in IR-associated comorbidities. We attempted to evaluate whether ET-1 also affects the long-chain fatty acid (LCFA) utilization in 3T3-L1 adipocytes. The effects of chronic ET-1 exposure on basal and insulin-stimulated LCFA uptake, and LCFA uptake kinetics were examined in 3T3-L1 adipocytes. Chronic exposure to ET-1 induced IR and suppressed basal and insulin-stimulated LCFA uptake. Given that insulin acutely stimulates LCFA uptake, there was dramatically similar trend of dose-response curves for ET-1-suppressed LCFA uptake, and also similar corresponding IC₅₀ values, between basal and insulin-stimulated states, reflecting that ET-1 predominantly suppresses basal LCFA uptake. Results of LCFA kinetics, western blots, and CD36 inhibition using sulfosuccinimidyl oleate (SSO) revealed that suppression of LCFA uptake by ET-1 is associated with downregulation of CD36. ET type A receptor (ET(A)R) antagonist BQ-610 reversed the IR induction and the ET-1-suppressed LCFA uptake. Exogenous replenishment of phosphatidylinositol (PI) 4, 5-bisphosphate (PIP₂) prevented IR induction, but not the suppression of LCFA uptake by ET-1. Pharmacological inhibition of the activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) completely blocked the ET-1-suppressed LCFA uptake. Serving as an inducer of IR, ET-1 also chronically suppresses LCFA uptake via PIP₂-independent and ERK-dependent pathway. The interplay between impaired glucose disposal and diminished LCFA utilization, induced by ET-1, could worsen the dysregulation of adipose metabolism and energy homeostasis in insulin-resistant states.
- Published
- 2011
18. Enhanced long-chain fatty acid uptake contributes to overaccumulation of triglyceride in hyperinsulinemic insulin-resistant 3T3-L1 adipocytes
- Author
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Ching Fai Kwok, Ying-Hsiu Lai, Yueh Chien, and Low-Tone Ho
- Subjects
medicine.medical_specialty ,MAP Kinase Signaling System ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Adipose tissue ,Biology ,Mice ,chemistry.chemical_compound ,Endocrinology ,Insulin resistance ,3T3-L1 Cells ,Hyperinsulinism ,Internal medicine ,Adipocyte ,medicine ,Hyperinsulinemia ,Animals ,Insulin ,Triglycerides ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Triglyceride ,Fatty Acids ,Fatty acid ,3T3-L1 ,medicine.disease ,Glucose ,chemistry ,lipids (amino acids, peptides, and proteins) ,Insulin Resistance ,Oxidation-Reduction ,Signal Transduction - Abstract
The precise pathogenesis of obesity remains controversial. In obesity, diminished adipose glucose utilization suggests that some other substrates may be responsible for the adipose triglyceride (TG) overaccumulation. Here we attempted to evaluate if long-chain fatty acid (LCFA) flux was modulated by a physiologically relevant condition of hyperinsulinemia in 3T3-L1 adipocytes and if the altered LCFA influx might eventually contribute to the TG overaccumulation in obesity. The effects of prolonged insulin exposure to adipocytes on basal, insulin-stimulated LCFA uptake as well as intracellular LCFA metabolism were measured. Prolonged insulin exposure was found to induce insulin resistance (IR) yet enhance basal and insulin-stimulated LCFA uptake in normoglycemic condition, and the addition of high glucose exacerbated these abnormalities of both glucose and LCFA influx. Along with the enhanced LCFA uptake was an increase in the rates of intracellular LCFA deposition and incorporation into TG; but a decrease was found in basal and insulin-suppressive LCFA oxidation, as well as in isoproterenol-induced fatty acid efflux. Inhibition of either phosphatidylinositol 3-kinase or mitogen-activated protein kinase (MAPK) pathway did not prevent the induction of IR, whereas the enhanced basal and insulin-stimulated LCFA uptake was abrogated by inhibition of MAPK pathway. In hyperinsulinemic insulin-resistant 3T3-L1 adipocytes, basal and insulin-stimulated LCFA uptake tends to increase via a MAPK-dependent mechanism. The increment of LCFA influx predominantly accounts for TG overaccumulation, but not for mitochondrial oxidation, and is prone to retain within adipocytes. These findings may interpret the plausible mechanism of pathogenesis for obesity in hyperinsulinemia-associated IR.
- Published
- 2010
19. Leptin increases endothelin type A receptor levels in vascular smooth muscle cells
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Tung Yueh Chuang, Yen Jie Lin, Ching Fai Kwok, Low-Tone Ho, Seng Wong Huang, Chi Chang Juan, and Chih Chen Lien
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Leptin ,medicine.medical_specialty ,Vascular smooth muscle ,Physiology ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,Immunoblotting ,Gene Expression ,Adipokine ,Biology ,Muscle, Smooth, Vascular ,Cell Line ,Iodine Radioisotopes ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Receptor ,Aorta ,media_common ,Leptin receptor ,Dose-Response Relationship, Drug ,Endothelin-1 ,Appetite ,Blotting, Northern ,Receptor, Endothelin A ,Endothelin 1 ,Rats ,Kinetics ,Endocrinology ,Mitogen-Activated Protein Kinases ,Endothelin receptor ,Cell Division ,Signal Transduction - Abstract
Leptin, one of the adipocyte-secreted peptides, is involved in the control of appetite and body weight. Several studies have demonstrated that plasma leptin levels are elevated in obese subjects and are positively correlated with body weight. The arterial endothelin (ET) system plays an important role in the regulation of vascular tone, and ET-1 overexpression may be involved in the pathogenesis of the hypertension associated with insulin resistance. This study was performed to explore the regulatory effects of leptin on ET receptor expression and ET binding in A10 vascular smooth muscle cells (VSMCs) by use of Northern blotting, immunoblotting, and a 125I-labeled ET-1 binding assay. The effect of leptin on ET receptor-mediated cell proliferation was also tested. The results showed that leptin caused a significant increase in [125I]-ET-1 binding, which was time- and dose-dependent. Immunoblotting showed that expression of the ET type A receptor (ETAR) in leptin (10−7 M)-treated cells was increased by up to 2.3-fold compared with controls. Levels of ETAR mRNA measured by Northern blotting were also increased by up to 2.2-fold in leptin (10−7 M)-treated cells. Pretreatment with an ERK inhibitor, PD-98059 (2.5 × 10−5 M), blocked the leptin-induced increase in 125I-ET-1 binding. Finally, ET-1 (10−7 M)-stimulated cell proliferation was enhanced by leptin (10−7 M) pretreatment, with a maximal increase of twofold compared with controls. In conclusion, leptin increases ETAR expression in VSMCs in a time- and dose-dependent manner. This effect is ERK dependent and is associated with increased ET-1-stimulated cell proliferation. These findings provide support for roles for leptin and the ET system in the pathogenesis of obesity-associated hypertension.
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- 2008
20. Endothelin-1 decreases CD36 protein expression in vascular smooth muscle cells
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Chi Chang Juan, Low-Tone Ho, and Ching Fai Kwok
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CD36 Antigens ,Endothelin Receptor Antagonists ,Male ,medicine.medical_specialty ,Vascular smooth muscle ,Physiology ,Endocrinology, Diabetes and Metabolism ,CD36 ,Down-Regulation ,Biology ,Muscle, Smooth, Vascular ,Protein expression ,Rats, Sprague-Dawley ,Physiology (medical) ,Internal medicine ,Gene expression ,medicine ,Animals ,Phosphorylation ,Scavenger receptor ,Extracellular Signal-Regulated MAP Kinases ,Cells, Cultured ,Receptors, Lipoprotein ,Endothelin-1 ,Vascular disease ,Endothelial Cells ,Transporter ,Protein-Tyrosine Kinases ,medicine.disease ,Endothelin 1 ,Rats ,Endocrinology ,biology.protein - Abstract
Recent studies have shown that CD36 plays important roles as a major scavenger receptor for oxidized low-density lipoproteins and as a crucial transporter for long-chain fatty acids. CD36 deficiency might be associated with insulin resistance and abnormal dynamics of long-chain fatty acids. Endothelin-1 (ET-1), which is synthesized and secreted by vascular endothelial cells, is the most potent endogenous vasoconstrictor known and also stimulates the proliferation of vascular smooth muscle cells (VSMCs) and thus is believed to play an important role in the development of various circulatory disorders, including hypertension and atherosclerosis. The aim of the present study was to investigate the regulatory effect of ET-1 on CD36 expression in cultured VSMCs. VSMCs were treated for different times (0–24 h) with a fixed concentration (100 nM) of ET-1 or with different concentrations (0–100 nM) for a fixed time (24 h); then CD36 expression was determined using Western blots. CD36 expression was significantly decreased by ET in a time- and dose-dependent manner. This inhibitory effect was prevented by the ETAreceptor antagonist BQ-610 (10 μM) but not the ETBreceptor antagonist BQ-788 (10 μM). To further explore the underlying mechanisms of ET-1 action, we examined the involvement of the tyrosine kinase-mediated and MAPK-mediated pathways. The inhibitory effect of ET-1 on CD36 protein expression was blocked by inhibition of tyrosine kinase activation by use of genistein (100 μM) and by the ERK inhibitor PD-98059 (75 μM) but not by the p38 MAPK inhibitor SB-203580 (20 μM). In conclusion, we have demonstrated that ET-1, acting via the ETAreceptor, suppresses CD36 protein expression in VSMCs by activation of the tyrosine kinase and ERK pathways.
- Published
- 2007
21. Effects of bariatric weight loss surgery on glucose metabolism, inflammatory cytokines, and serum tartrate-resistant acid phosphatase 5a in obese Chinese adults
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Low-Tone Ho, Anthony J. Janckila, Wei Jei Lee, Tsu Yi Chao, Chun Jui Huang, Kuang Chung Shih, Yu-Ching Chou, and Ching Fai Kwok
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0301 basic medicine ,Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Clinical Biochemistry ,Acid Phosphatase ,Bariatric Surgery ,030209 endocrinology & metabolism ,Carbohydrate metabolism ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Asian People ,Weight loss ,Internal medicine ,Diabetes mellitus ,Weight Loss ,medicine ,Glucose homeostasis ,Humans ,Obesity ,Tartrate-resistant acid phosphatase ,Inflammation ,biology ,business.industry ,Tartrate-Resistant Acid Phosphatase ,Biochemistry (medical) ,C-reactive protein ,General Medicine ,medicine.disease ,Lipids ,Isoenzymes ,030104 developmental biology ,Endocrinology ,C-Reactive Protein ,Case-Control Studies ,biology.protein ,Cytokines ,Female ,medicine.symptom ,Metabolic syndrome ,Insulin Resistance ,business - Abstract
Background We determined effects of bariatric weight loss surgery on serum tartrate-resistant acid phosphatase 5a (TRACP 5a), inflammatory cytokines and glucose homeostasis in severely obese Chinese adults. Methods Severely obese adults undergoing bariatric surgery were recruited. Anthropometry, insulin resistance (IR), inflammatory markers and serum TRACP 5a were measured at baseline and 3, 6 and 12 months postoperatively. Results Data of 93 patients, including 69 non-diabetic (non-DM group) and 24 diabetic (DM group), were analyzed. Anthropometry decreased significantly at 3 months postoperatively in both groups; low-density lipoprotein cholesterol decreased obviously at 3, 6 and 12 months in non-DM group, while improving significantly at 6 and 12 months in DM group. Homeostasis model assessment for IR (HOMA-IR) improved significantly at 3, 6 and 12 months in non-DM group and 12 months in DM group. In DM group, C-reactive protein (CRP) decreased significantly at 3 months postoperatively and inflammatory markers interleukin-6 (IL-6) and TRACP 5a improved at 6 months postoperatively; in non-DM group, serum TRACP 5a decreased obviously at 12 months postoperatively without significant changes in CRP and IL-6. Conclusion Weight reduction by bariatric surgery decreases anthropometry, IR, lipids and inflammatory markers in severely obese Chinese adults.
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- 2015
22. Major urinary protein 1 interacts with cannabinoid receptor type 1 in fatty acid-induced hepatic insulin resistance in a mouse hepatocyte model
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Ching-Fai Kwok, Tzung-Yan Lee, Chin-Chang Chen, Kuang-Chung Shih, Yung-Pei Hsu, Low-Tone Ho, and Yan-Jie Lin
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AM251 ,Male ,medicine.medical_specialty ,Blotting, Western ,Biophysics ,Biology ,Diet, High-Fat ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Models, Biological ,Mice ,Insulin resistance ,Piperidines ,Receptor, Cannabinoid, CB1 ,Internal medicine ,Cannabinoid receptor type 1 ,medicine ,Animals ,Gene Silencing ,Molecular Biology ,chemistry.chemical_classification ,Fatty Acids ,Fatty acid ,Proteins ,Cell Biology ,medicine.disease ,Mice, Inbred C57BL ,Insulin receptor ,Endocrinology ,chemistry ,Gluconeogenesis ,Liver ,biology.protein ,Hepatocytes ,Phosphorylation ,Pyrazoles ,Insulin Resistance ,Phosphoenolpyruvate carboxykinase ,Reactive Oxygen Species ,medicine.drug - Abstract
Hepatic insulin resistance (HIR) is a metabolic abnormality characterized by increased gluconeogenesis which usually contributes from an elevation of free fatty acids. Cannabinoid receptor type 1 (CB1R) and major urinary protein 1 (MUP1) are thought to play pivotal roles in mitochondrial dysfunction, liver steatosis and insulin resistance. The aim of this study was to explore the role of MUP1 in CB1R-mediated HIR through the dysregulation of mitochondrial function in AML12 mouse hepatocytes challenged with high concentration of free fatty acids (HFFA). Firstly we observed that treatment of AM251, a selective CB1R antagonist, obviously reversed the HFFA-induced reduction of MUP1 protein expression both in vivo and in vitro. Additionally, our results revealed that AM251 also reverted HFFA-mediated decrease of the mRNA level of mitochondrial biogenesis-related factors, mtDNA amount, ATP production, mitochondrial respiratory complexes-I and -III, and mitochondrial membrane potential, thus consequently might correlate with a parallel reduction of ROS production. Meanwhile, AM251 attenuated HFFA-induced impairment of insulin signaling phosphorylation and elevation of phosphoenolpyrvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), two key enzymes of gluconeogenesis. Silence of MUP1 gene abolished the inhibitory effect of AM251 on HFFA-mediated elevation of PEPCK and G6Pase expression, whereas the suppression of insulin signaling and mRNA level of mitochondrial biogenesis-related factors were only partially recovered. Altogether, these findings suggest that the anti-HIR effect of AM251 via improvement of mitochondrial functions might occur in a MUP1-dependent manner.
- Published
- 2015
23. Cannabinoid receptor type 1 mediates high-fat diet-induced insulin resistance by increasing forkhead box O1 activity in a mouse model of obesity
- Author
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Chin-Chang Chen, Kuang-Chung Shih, Yung-Pei Hsu, Tzung-Yan Lee, Ching-Fai Kwok, Yan-Jie Lin, and Low-Tone Ho
- Subjects
0301 basic medicine ,AM251 ,Male ,medicine.medical_specialty ,NF-E2-Related Factor 1 ,FOXO1 ,Citrate (si)-Synthase ,Diet, High-Fat ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Insulin resistance ,Piperidines ,Internal medicine ,Genetics ,medicine ,Citrate synthase ,Animals ,Carnitine ,Obesity ,Receptors, Cannabinoid ,Cannabinoid Receptor Agonists ,biology ,Forkhead Box Protein O1 ,High Mobility Group Proteins ,nutritional and metabolic diseases ,General Medicine ,TFAM ,medicine.disease ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Insulin receptor ,030104 developmental biology ,Endocrinology ,030220 oncology & carcinogenesis ,biology.protein ,Homeostatic model assessment ,Pyrazoles ,Insulin Resistance ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Hepatic glucose production is promoted by forkhead box O1 (FoxO1) under conditions of insulin resistance. The overactivity of cannabinoid receptor type 1 (CB1R) partly causes increased liver fat deposits and metabolic dysfunction in obese rodents by decreasing mitochondrial function. The aim of the present study was to investigate the role of FoxO1 in CB1R-mediated insulin resistance through the dysregulation of mitochondrial function in the livers of mice with high-fat diet (HFD)-induced obesity. For this purpose, male C57BL/6 mice were randomly assigned to groups and either fed a standard diet (STD), a HFD, or a HFD with 1-week treatment of the CB1R inverse agonist, AM251, at 1 or 5 mg/kg. For in vitro experiments, AML12 hepatocytes were incubated with FoxO1 siRNA prior to challenge with arachidonyl-2'-chloroethylamide (ACEA) or a high concentration of free fatty acids (HFFA). Plasma parameters were analyzed using colorimetric methods. Liver histopathology and hepatic status markers were examined. The HFD-fed mice exhibited an increase in CB1R levels in the liver. Moreover, in response to increased hepatic oxidative stress, the HFD-fed mice also displayed hepatic mitochondrial dysfunction, as indicated by the decreased mRNA levels of carnitine palmitoyltransferase-1 (CPT-1), mitochondrial transcription factor A (TFAM), nuclear respiratory factor-1 (NRF-1) and citrate synthase. On the contrary, these effects in the HFD-fed mice were reversed by treatment with 5 mg/kg AM251. The administration of AM251 suppressed the induction of FoxO1, phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) expression in the livers of the mice fed a HFD by enhancing the phosphorylation of insulin signaling cascades thus, further lowering the high level of the homeostatic model assessment of insulin resistance (HOMA‑IR) index. In our in vitro experiments, transfection with FoxO1 siRNA prevented the HFFA- and ACEA-induced decrease in the gene expression of mitochondrial biogenesis-related factors, and abrogated the HFFA- and ACEA-induced increase in PEPCK and G6Pase expression. Taken together, our findings suggest that the anti-insulin resistance effect of AM251, which leads to an improvement of mitochondrial function in hepatic steatosis, is mediated through FoxO1.
- Published
- 2015
24. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome
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Ching Fai Kwok, Yan Jie Lin, Chin Chang Chen, Kuang Chung Shih, Chi Chang Juan, Low-Tone Ho, and Yung Pei Hsu
- Subjects
MAPK/ERK pathway ,medicine.medical_specialty ,Endothelium ,medicine.medical_treatment ,Biophysics ,Diet, High-Fat ,Biochemistry ,Muscle, Smooth, Vascular ,Rats, Sprague-Dawley ,Insulin resistance ,Internal medicine ,medicine ,Hyperinsulinemia ,Animals ,Insulin ,Phosphorylation ,Molecular Biology ,Protein kinase B ,Cells, Cultured ,biology ,Endothelin-1 ,Chemistry ,Cell Biology ,medicine.disease ,Atherosclerosis ,Endothelin 1 ,Rats ,Insulin receptor ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,Hypertension ,cardiovascular system ,biology.protein ,Insulin Resistance - Abstract
Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ETAR during insulin resistance, ETAR expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ETAR expression, but not ETBR, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ETAR pathway suppressed insulin-induced AKT activation, whereas remained insulin-induced ERK activation. ET-1 and insulin synergistically potentiated migration and proliferation mainly through ETAR/ERK dependent pathway, which is dominant in VSMCs during modest insulin resistance syndrome. Therefore, ET-1 and ETAR are potential targets responsible for the observed synergism effect in the hypertensive atherosclerotic process through enhancement of ET-1 binding, ET-1 binding, ETAR expression, and ET-1-induced mitogenic actions in aortic VSMCs.
- Published
- 2015
25. Visfatin Promotes Monocyte Adhesion by Upregulating ICAM-1 and VCAM-1 Expression in Endothelial Cells via Activation of p38-PI3K-Akt Signaling and Subsequent ROS Production and IKK/NF-κB Activation.
- Author
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Yu-Ting Lin, Luen-Kui Chen, Deng-Yuan Jian, Ting-Chia Hsu, Wei-Chih Huang, Tse-Ting Kuan, Shao-Yun Wu, Ching-Fai Kwok, Low-Tone Ho, and Chi-Chang Juan
- Subjects
MONOCYTES ,ENDOTHELIAL cells ,ACTIVE oxygen in the body ,PHOSPHORYLATION ,METABOLIC disorders - Abstract
Background/Aims: Visfatin is known to act as a mediator in several metabolic disorders, such as obesity, diabetes, and cardiovascular diseases. This study aimed to investigate the effect of visfatin on the adhesion of THP-1 monocytes to human vascular endothelial cells and the underlying mechanism. Methods: Monocytes adhesion to endothelial cells was determined by using fluorescence-labeled monocytes. ICAM-1 and VCAM-1 expression in endothelial cells were measured by western blotting. Production of reactive oxygen species (ROS) was measured by using a fluorescent dye. The amounts of nuclear factor-kappa B (NF-κB) and phosphorylation of inhibitory factor of NF-κB (IκB) were determined by using western blot analysis. The translocation of NF-κB from the cytoplasm to the nucleus was determined by using immunofluorescence. Results: Here we showed that visfatin significantly caused the upregulation of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells, as well as enhanced monocyte adhesion to endothelial cells. Moreover, we found that inhibition of PI3K, Akt, and p38 MAPK activation significantly prevented visfatin-enhanced expression of ICAM-1 and VCAM-1 and monocyte adhesion to endothelial cells. Visfatin enhanced ROS production and IKK/NF-кB activation and then led to upregulation of ICAM-1 and VCAM-1 and enhanced monocyte adhesion to endothelial cells. These effects were also p38/PI3K/Akt-dependent. Conclusion: These results demonstrated that visfatin promoted monocyte-endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression via the activation of p38/PI3K/Akt signaling and downstream ROS production and IKK/NF-кB activation. [ABSTRACT FROM AUTHOR]
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- 2019
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26. Angiotensin II Enhances Insulin Sensitivity in Vitro and in Vivo
- Author
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Chi Chang Juan, Low-Tone Ho, Wei-Ming Yang, Chih Ling Chang, Ching Fai Kwok, Pei-Hsuan Ho, Yueh Chien, Ying-Hsiu Lai, and Liang-Yi Wu
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Monosaccharide Transport Proteins ,medicine.medical_treatment ,Glucose uptake ,Gene Expression ,Muscle Proteins ,Protein Serine-Threonine Kinases ,Receptor, Angiotensin, Type 2 ,Losartan ,Receptor, Angiotensin, Type 1 ,Rats, Sprague-Dawley ,Endocrinology ,Insulin resistance ,Proto-Oncogene Proteins ,Internal medicine ,Adipocytes ,medicine ,Animals ,Insulin ,Phosphorylation ,Glucose tolerance test ,Glucose Transporter Type 4 ,Angiotensin II receptor type 1 ,biology ,medicine.diagnostic_test ,Reverse Transcriptase Polymerase Chain Reaction ,Angiotensin II ,Glucose transporter ,Drug Synergism ,Glucose Tolerance Test ,medicine.disease ,Receptor, Insulin ,Rats ,Insulin receptor ,Glucose ,cardiovascular system ,biology.protein ,sense organs ,Insulin Resistance ,Angiotensin II Type 1 Receptor Blockers ,Proto-Oncogene Proteins c-akt ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction ,circulatory and respiratory physiology - Abstract
The renin-angiotensin system plays a critical role in the pathogenesis of obesity, obesity-associated hypertension, and insulin resistance. However, the biological actions of angiotensin II (AII) on insulin sensitivity remain controversial. Because angiotensinogen and AII receptors are expressed on adipose tissue, we investigated the effect of AII on the insulin sensitivity of isolated rat adipocytes. The results of a receptor binding assay showed the maximal AII binding capacity of adipocytes to be 8.3 ± 0.9 fmol/7 × 106 cells and the dissociation constant to be 2.72 ± 0.11 nm. Substantial expression of both type 1 and 2 AII (AT1 and AT2) receptors was detected by RT-PCR. AII had no effect on basal glucose uptake, but significantly potentiated insulin-stimulated glucose uptake; this effect was abolished by the AT1 antagonist, losartan. In addition, AII did not alter the insulin binding capacity of adipocytes, but increased insulin-stimulated tyrosine phosphorylation of the insulin receptor β-subunit, Akt phosphorylation, and translocation of glucose transporter 4 to the plasma membrane. AII potentiated insulin-stimulated glucose uptake through the AT1 receptor and by alteration of the intracellular signaling of insulin. Intraperitoneal injection of Sprague Dawley rats with AII increased insulin sensitivity in vivo. In conclusion, we have shown that AII enhances insulin sensitivity both in vitro and in vivo, suggesting that dysregula-tion of the insulin-sensitizing effect of AII may be involved in the development of insulin resistance.
- Published
- 2005
27. Diffuse soft tissue emphysema in anorexia nervosa: A case report
- Author
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Low-Tone Ho, Ching-Fai Kwok, Hong-Da Lin, Kam-Tsun Tang, and Liang-Yu Lin
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Adult ,medicine.medical_specialty ,Anorexia Nervosa ,Body Mass Index ,medicine ,Humans ,Pneumomediastinum ,Mediastinal Emphysema ,business.industry ,Respiratory disease ,Prognosis ,medicine.disease ,Subcutaneous Emphysema ,Surgery ,Hospitalization ,Psychiatry and Mental health ,Retropneumoperitoneum ,Anorexia nervosa (differential diagnoses) ,Female ,Amenorrhea ,medicine.symptom ,business ,Complication ,Body mass index ,Subcutaneous emphysema - Abstract
Objective Anorexia nervosa (AN) is an eating disorder that occurs mainly among young females and its prevalence has increased in recent decades. Methods We reported a patient with AN with spontaneous diffuse soft tissue emphysema and bicytopenia, both of which are very rare complications of AN. Our patient, a 20-year-old woman, had lost 41.6% of her previous body weight within 9 months. Her body mass index was 10.8 and amenorrhea had persisted for 5 months. Results After admission, she was diagnosed with AN-restrictive subtype. She was noted to have crunching sounds in the neck and upper chest wall during hospitalization. A chest X-ray and chest computed tomography scan both revealed diffuse soft tissue emphysema including subcutaneous emphysema, pneumomediastinum, and pneumoretroperitoneum. Discussion Diffuse soft tissue emphysema improved gradually and completely resolved on the 21st day of hospitalization. This condition seems to be benign and only a short period of hospitalization is required. © 2005 by Wiley Periodicals, Inc.
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- 2005
28. Using proteomics to discover novel biomarkers for fatty liver development and response to CB1R antagonist treatment in an obese mouse model
- Author
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Yung-Pei Hsu, Chin-Chang Chen, Yan-Jie Lin, Low-Tone Ho, Kuang-Chung Shih, Ching-Fai Kwok, and Tzung-Yan Lee
- Subjects
Male ,Proteomics ,0301 basic medicine ,AM251 ,Epoxide hydrolase 2 ,medicine.medical_specialty ,Protein subunit ,Mice, Obese ,Biology ,Mitochondrion ,Diet, High-Fat ,Biochemistry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Piperidines ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Animals ,Receptors, Cannabinoid ,Cannabinoid Receptor Antagonists ,Molecular Biology ,ATP synthase ,Fatty liver ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,biology.protein ,Pyrazoles ,Steatosis ,Biomarkers ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Over activity of cannabinoid receptor type 1 (CB1R) plays a key role in increasing the incidence of obesity-induced non-alcoholic fatty liver disease. Tissue proteome analysis has been applied to investigate the bioinformatics regarding the mode of action and therapeutic mechanism. The aim of this study was to explore the potential pathways altered with CB1R in obesity-induced fatty liver. Male C57BL/6 mice were fed either a standard chow diet (STD) or a high-fat diet (HFD) with or without 1-week treatment of CB1R inverse agonist AM251 at 5 mg/kg. Then, liver tissues were harvested for 2DE analysis and protein profiles were identified by using MALDI-MS. Results showed that eight of significantly altered protein spots at the level of changes > twofold were overlapped among the three groups, naming major urinary protein 1, ATP synthase subunit β, glucosamine-fructose-6-phosphate aminotransferase 1, zine finger protein 2, s-adenosylmethionine synthase isoform type-1, isocitrate dehydrogenase subunit α, epoxide hydrolase 2 and 60S acidic ribosomal protein P0. These identified proteins were involved in glucose/lipid metabolic process, xenobiotic metabolic system, and ATP synthesized process in mitochondria. Based on the findings, we speculated that CB1R blockade might exert its anti-metabolic disorder effect via improvement of mitochondrial function in hepatic steatosis in HFD condition.
- Published
- 2017
29. The ankle brachial index is associated with prognosis in patients with diabetic kidney disease
- Author
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Harn Shen Chen, Liang Yu Lin, Justin G.S. Won, Li Hsin Chang, Hong Da Lin, Chia Huei Chu, and Ching Fai Kwok
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Renal function ,Type 2 diabetes ,chemistry.chemical_compound ,Peripheral Arterial Disease ,Endocrinology ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Albuminuria ,Humans ,Ankle Brachial Index ,Diabetic Nephropathies ,Risk factor ,Aged ,Retrospective Studies ,Creatinine ,business.industry ,Incidence ,Type 2 Diabetes Mellitus ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Surgery ,chemistry ,Diabetes Mellitus, Type 2 ,Female ,Glycated hemoglobin ,medicine.symptom ,business - Abstract
Peripheral arterial disease (PAD) could be an additional risk factor for the clinical outcomes in different populations. The purpose of this study was to evaluate the influence of PAD on patients with diabetic kidney disease.362 persons with type 2 diabetes were followed-up for a mean 4.8 years grouped by ankle brachial index (ABI) (0.9 vs. ≧0.9) and albuminuria (with or without). Primary and secondary outcomes were composite events (all-cause mortality, hospitalization for coronary artery disease, stroke, re-vascularization, amputation, and diabetic foot) and all-cause mortality.Inter-group differences in duration of diabetes, glycated hemoglobin, creatinine, and estimated glomerular filtration rate were significant. During the follow-up period, 53 composite events were recorded (14.7%) and 13 (3.5%) individuals died. Subjects with albuminuria plus ABI0.9 had higher risk of composite events than those with albuminuria but normal ABI (p0.05). The only trend difference between the two groups was in all-cause mortality. Albuminuria plus ABI0.9 was associated with risk of composite events (hazard ratio [HR] 4.20, 95% confidence interval [CI] 1.77-9.92, p=0.001) and all-cause mortality (HR 17.77, 95% CI 1.93-162.20, p=0.011).PAD might be an additional risk factor for adverse outcomes in patients with diabetic kidney disease. Further prospective data are required to validate this conclusion.
- Published
- 2014
30. Angiotensin II enhances endothelin-1-induced vasoconstriction through upregulating endothelin type A receptor
- Author
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Yung-Pei Hsu, Kuang-Chung Shih, Yan-Jie Lin, Low-Tone Ho, Chi Chang Juan, Chin-Chang Chen, and Ching-Fai Kwok
- Subjects
MAPK/ERK pathway ,Male ,medicine.medical_specialty ,Vascular smooth muscle ,MAP Kinase Signaling System ,Pyridines ,Myocytes, Smooth Muscle ,Biophysics ,Aorta, Thoracic ,Angiotensin II Type 2 Receptor Blockers ,Biochemistry ,Losartan ,Cell Line ,Rats, Sprague-Dawley ,Internal medicine ,medicine ,Animals ,Receptor ,Molecular Biology ,Protein kinase C ,Protein Kinase C ,Endothelin-1 ,Chemistry ,Angiotensin II ,Imidazoles ,Cell Biology ,Receptor, Endothelin A ,Endothelin 1 ,Rats ,Up-Regulation ,Endocrinology ,Vasoconstriction ,cardiovascular system ,medicine.symptom ,Endothelin receptor ,Angiotensin II Type 1 Receptor Blockers ,hormones, hormone substitutes, and hormone antagonists - Abstract
Endothelin-1 (ET-1) is the most potent vasoconstrictor by binding to endothelin receptors (ETAR) in vascular smooth muscle cells (VSMCs). The complex of angiotensin II (Ang II) and Ang II type one receptor (AT1R) acts as a transient constrictor of VSMCs. The synergistic effect of ET-1 and Ang II on blood pressure has been observed in rats; however, the underlying mechanism remains unclear. We hypothesize that Ang II leads to enhancing ET-1-mediated vasoconstriction through the activation of endothelin receptor in VSMCs. The ET-1-induced vasoconstriction, ET-1 binding, and endothelin receptor expression were explored in the isolated endothelium-denuded aortae and A-10 VSMCs. Ang II pretreatment enhanced ET-1-induced vasoconstriction and ET-1 binding to the aorta. Ang II enhanced ETAR expression, but not ETBR, in aorta and increased ET-1 binding, mainly to ETAR in A-10 VSMCs. Moreover, Ang II-enhanced ETAR expression was blunted and ET-1 binding was reduced by AT1R antagonism or by inhibitors of PKC or ERK individually. In conclusion, Ang II enhances ET-1-induced vasoconstriction by upregulating ETAR expression and ET-1/ETAR binding, which may be because of the AngII/Ang II receptor pathways and the activation of PKC or ERK. These findings suggest the synergistic effect of Ang II and ET-1 on the pathogenic development of hypertension.
- Published
- 2014
31. Abnormal cardiovascular reflex tests are predictors of mortality in Type 2 diabetes mellitus
- Author
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Low-Tone Ho, Y. S. Lee, H. S. Chen, M. J. Weih, S. H. Lin, B. I. Kuo, Ching-Fai Kwok, Chii-Min Hwu, S. C. Chiang, L. C. Hsiao, and S. H. Lee
- Subjects
Diabetic Autonomic Neuropathy ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Mortality rate ,Type 2 Diabetes Mellitus ,Type 2 diabetes ,medicine.disease ,Surgery ,Endocrinology ,Blood pressure ,Internal medicine ,Predictive value of tests ,Diabetes mellitus ,Internal Medicine ,medicine ,Cardiology ,business ,Survival rate - Abstract
SUMMARY Aims To determine whether diabetic autonomic neuropathy is an important factor contributing to mortality in Type 2 diabetes mellitus. Methods Between 1989 and 1993, 431 men and 181 women with Type 2 diabetes were given diabetic autonomic neuropathy cardiovascular reflex (CVR) tests. These subjects were followed for the subsequent 5–9 years to assess mortality rates. Results The prevalence rate of abnormal CVR tests was 46.1% in patients with the history of diabetes less than 5 years and up to 69.4% when the history of diabetes exceeded 20 years. During the follow-up period from 1 January 1989 to 31 December 1997 (mean 7.7 years), a total of 135 participants died. The 8-year survival rate for patients with abnormal CVR tests was 63.6% in males and 76.4% in females, compared with 80.9 and 93.3% for patients with normal CVR tests. The results were grouped as: group 1, normal CVR tests without postural hypotension (PHT); group 2, normal CVR tests with PHT; group 3, abnormal CVR tests without PHT; and group 4, abnormal CVR tests with PHT. The 8-year survival rate was 85.4% in group 1, 80.9% in group 2, 74.5% in group 3 and 61.1% in group 4. Conclusion Type 2 diabetic patients with abnormal CVR tests may have increased mortality, and those combined with postural hypotension have higher mortality than those without. Abnormal CVR tests may be important predictors of mortality in Type 2 diabetes mellitus.
- Published
- 2001
32. Growth inhibition of cultured smooth muscle cells by corrosion products of 316 L stainless steel wire
- Author
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Ching Fai Kwok, Chun Che Shih, Yuh-Lien Chen, Jeng Shong Shih, Chun Ming Shih, Shing Jong Lin, and Yea Yang Su
- Subjects
Materials science ,Vascular smooth muscle ,Biocompatibility ,Cell growth ,Metallurgy ,Biomedical Engineering ,chemistry.chemical_element ,Biomaterial ,Cell morphology ,Corrosion ,Biomaterials ,Nickel ,chemistry.chemical_compound ,chemistry ,Growth inhibition ,Nuclear chemistry - Abstract
The potential cytotoxicity on vascular smooth muscle cells of corrosion products from 316 L stainless steel, one of most popular biomaterials of intravascular stents, has not been highlighted. In this investigation, 316 L stainless steel wires were corroded in Dulbecco's modified eagle's medium with applied constant electrochemical breakdown voltage, and the supernatant and precipitates of corrosion products were prepared as culture media. The effects of different concentrations of corrosion products on the growth of rat aortic smooth muscle cells were conducted with the [3H]-thymidine uptake test and cell cycle sorter. Both the supernatant and precipitates of corrosion products were toxic to the primary culture of smooth muscle cells. The growth inhibition was correlated well with the increased nickel ions in the corrosion products when nickel concentration was above 11.7 ppm. The corrosion products also changed cell morphology and induced cell necrosis. The cell growth inhibition occurred at the G0/G1 to S transition phase. Similar to our recent study of nitinol stent wire, the present investigation also demonstrated the cytotoxicity of corrosion products of 316 L stainless steel stent wire on smooth muscle cells, which might affect the poststenting vascular response.
- Published
- 2001
33. Linoleic acid and oleic acid increase the endothelin-1 binding and action in cultured rat aortic smooth muscle cells
- Author
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Ching Fai Kwok, Chii-Min Hwu, Kuang-Chung Shih, and Low-Tone Ho
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Linoleic acid ,Fatty Acids, Nonesterified ,Biology ,Muscle, Smooth, Vascular ,Linoleic Acid ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Endocrinology ,NEFA ,Internal medicine ,medicine ,Animals ,Receptor ,Aorta ,Cells, Cultured ,Endothelin-1 ,Biological activity ,Endothelin 1 ,In vitro ,Rats ,Oleic acid ,chemistry ,Thymidine ,Oleic Acid ,Protein Binding - Abstract
An increase in circulating non-esterified fatty acids (NEFA) has been observed in patients with poorly controlled diabetes mellitus. To investigate whether fatty acids will affect the endothelin-1 (ET-1) receptor and thus contribute to the acceleration of atherosclerosis in diabetic patients, cultured rat aortic smooth muscle cells (SMC) were maintained in media containing higher (similar to those in diabetic patients) concentrations of oleic acid (OA) or linoleic acid (LA). The ET-1 binding and ET-1-stimulated thymidine uptake were then examined. We found that cells treated with OA (500 micromol/L) or LA (250 micromol/L) showed a significant increase in ET-1 receptor amount as demonstrated by Scatchard analysis (Bmax: 7.40 +/- 1.04 v 2.71 +/- 0.54 fmol/mg and 5.00 +/- 1.00 v 3.32 +/- 0.70 fmol/mg, respectively). No change in binding affinity was found. Moreover, both the basal and ET-1-stimulated thymidine uptake were enhanced by treatment with either LA (basal, 11,367 +/- 4,117 cpm/mg; LA, 13,933 +/- 4,003 cpm/mg; ET-1 (10(-8)), 16,931 +/- 4,412 cpm/mg; LA +/- ET-1 (10(-8)), 28,855 +/- 5,217 cpm/mg) or OA (basal, 4,912 +/- 1,193 cpm/mg, OA, 8,027 +/- 1,318 cpm/mg; ET-1 (10(-8)) 9,947 +/- 2,520 cpm/mg; OA + ET-1 (10(-8)), 16,761 +/- 1,740 cpm/mg). This enhancement in thymidine uptake was associated with an increase in cell number. Because ET-1 and its receptor are involved in atherogenesis, our findings suggested that increase in circulating NEFA may contribute to the acceleration of atherosclerosis in diabetic patients. Further studies to confirm its role in the vascular wall are warranted.
- Published
- 2000
34. Using semi-automated oscillometric blood pressure measurement in diabetic patients and their offspring
- Author
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Chin-Sung Kuo, Ching Fai Kwok, Chii-Min Hwu, Sheng-Hung Lee, Li-Chuan Hsiao, Low-Tone Ho, and Mei-Jy Weih
- Subjects
Adult ,Male ,medicine.medical_specialty ,Systole ,Intraclass correlation ,Endocrinology, Diabetes and Metabolism ,Diastole ,Blood Pressure ,Sphygmomanometer ,Nuclear Family ,Impaired glucose tolerance ,Automation ,Diabetes mellitus genetics ,Endocrinology ,Oscillometry ,Diabetes mellitus ,Internal medicine ,Glucose Intolerance ,Diabetes Mellitus ,Internal Medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,business.industry ,Blood Pressure Determination ,Middle Aged ,Sphygmomanometers ,medicine.disease ,Blood Pressure Monitors ,Surgery ,Blood pressure ,Cardiology ,Regression Analysis ,Female ,business - Abstract
To determine whether a semi-automatic oscillometric blood pressure (BP) monitor Dinamap 1846SX (DIN) can replace the standard mercury sphygmomanometer (SMS) for BP measurements in diabetic patients and their offspring, we compared SMS with DIN in 105 diabetic patients and their families. Their mean age was 50.6 (range 24-86) years, of whom 41 had diabetes mellitus (DM), 32 impaired glucose tolerance and 32 non-DM. After resting quietly for 10 min, their right arm BP were measured twice with each device at random and with 1-min intervals between each measurement. Agreement between measurements was tested by plotting the differences between the methods against means and by intraclass correlation coefficient (r(I)). The DIN was also evaluated by the criteria of American Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society (BHS) criteria and clinical criteria of O'Brien. All measurements by DIN [first readings or averaged readings of duplicate measurements of systolic BP (SBP) or diastolic BP (DBP)] satisfied the AAMI criteria and had good agreement with SMS (r(I)=. 951 for SBP and r(I)=.905 for DBP). The first readings of systolic BP measured by DIN vs. SMS failed to satisfy the criteria by O'Brien and reached BHS grade C level. Other measurements passed the limits of O'Brien and reached BHS grade A or B. In conclusion, averaged readings of duplicate BP measurements by DIN are interchangeable with that by SMS in Chinese diabetic patients and their offspring. Only one single DIN measurement is not acceptable for clinical application.
- Published
- 2000
35. Combined use of insulin and endothelin-1 causes decrease of protein expression of ?-subunit of insulin receptor, insulin receptor substrate-1, and insulin-stimulated glucose uptake in rat adipocytes
- Author
-
Low-Tone Ho, Ching-Fai Kwok, and Kuang-Chung Shih
- Subjects
medicine.medical_specialty ,biology ,Chemistry ,Glucose uptake ,Insulin ,medicine.medical_treatment ,Cell Biology ,medicine.disease ,Biochemistry ,IRS2 ,IRS1 ,Insulin receptor ,Insulin resistance ,Endocrinology ,Internal medicine ,Insulin receptor substrate ,medicine ,biology.protein ,Molecular Biology ,Insulin-like growth factor 1 receptor - Abstract
Previously, we reported that insulin-stimulated glucose uptake (ISGU) can be inhibited by endothelin (ET-1). However, the mechanism by which ET-1 impairs ISGU in adipocytes remains unclear. This study investigated the effects of ET-1 on insulin action in rat adipocytes in order to elucidate the molecular mechanism of action of ET-1 on ISGU. The results show that ISGU was increased fivefold after 3-h treatment with 1 nM insulin. Treatment with 100 nM ET-1 had no effect on basal glucose uptake. However, ET-1 inhibited approximately 25% of ISGU and 20% of insulin binding after 3-h treatment in the presence of 1 nM insulin. Expression of the beta-subunit of the insulin receptor (IRbeta) and the insulin receptor substrate-1 (IRS-1) in adipocytes was not significantly affected by 1 nM insulin or by 100 nM ET-1, even after 3-h treatment. However, expressions of IRbeta and IRS-1 were dramatically decreased in a dose- and time-dependent manner when adipocytes were treated with both insulin and ET-1. Approximately 50% of IRbeta and 65% of IRS-1 expression levels were suppressed when adipocytes were simultaneously treated with both 1 nM insulin and 100 nM ET-1 for 3 h. These results suggest that the inhibitory effect of ET-1 on ISGU may be mediated via the insulin receptor and suppression of IRbeta/IRS-1 expression.
- Published
- 2000
36. The cytotoxicity of corrosion products of nitinol stent wire on cultured smooth muscle cells
- Author
-
Yea Yang Su, Ching Fai Kwok, Chun Che Shih, Gaston J. C. Wu, Kwok Hung Chung, Yuh-Lien Chen, Shing Jong Lin, and Lai St
- Subjects
Neointimal hyperplasia ,Materials science ,Vascular smooth muscle ,Biocompatibility ,Metallurgy ,Biomedical Engineering ,medicine.disease ,Cell morphology ,Corrosion ,Biomaterials ,chemistry.chemical_compound ,chemistry ,Cell culture ,medicine ,Biophysics ,Growth inhibition ,Cytotoxicity - Abstract
Although nitinol is one of most popular materials of intravascular stents, there are still few confirmative biocompatibility data available, especially in vascular smooth muscle cells. In this report, the nitinol wires were corroded in Dulbecco's modified Eagle's medium with constant electrochemical breakdown voltage and the supernatant and precipitates of corrosion products were prepared as culture media. The dose and time effects of different concentrations of corrosion products on the growth and morphology of smooth muscle cells were evaluated with [(3)H]-thymidine uptake ratio and cell cycle sorter. Both the supernatant and precipitate of the corrosive products of nitinol wire were toxic to the primary cultured rat aortic smooth muscle cells. The growth inhibition was correlated well with the increased concentrations of the corrosion products. Although small stimulation was found with released nickel concentration of 0.95 +/- 0.23 ppm, the growth inhibition became significant when the nickel concentration was above 9 ppm. The corrosion products also altered cell morphology, induced cell necrosis, and decreased cell numbers. The cell replication was inhibited at the G0-G1 to S transition phase. This was the first study to demonstrate the cytotoxicity of corrosion products of current nitinol stent wire on smooth muscle cells, which might affect the postimplantation neointimal hyperplasia and the patency rate of cardiovascular stents.
- Published
- 2000
37. Exogenous hyperinsulinemia causes insulin resistance, hyperendothelinemia, and subsequent hypertension in rats
- Author
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Low-Tone Ho, Ching Fai Kwok, Jing Cheng Perng, Chi Chang Juan, You Chung Chou, and Victor S. Fang
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Blood Pressure ,Rats, Sprague-Dawley ,Insulin Infusion Systems ,Endocrinology ,Insulin resistance ,Hyperinsulinism ,Internal medicine ,Blood plasma ,Adipocytes ,medicine ,Hyperinsulinemia ,Animals ,Hypoglycemic Agents ,Insulin ,Pancreatic hormone ,Endothelin-1 ,business.industry ,Cell Membrane ,Glucose transporter ,Glucose Tolerance Test ,medicine.disease ,Rats ,Blood pressure ,Basal (medicine) ,Hypertension ,Endothelium, Vascular ,Insulin Resistance ,business - Abstract
In many clinical and animal studies, hypertension and insulin resistance coexist, but their mechanistic relationship is unclear. We explored the causal link between these two parameters in a rat model with chronic hyperinsulinemia induced with human insulin (1 U/d) released from subcutaneously implanted minipumps. Rats with saline minipumps served as a control. During the first experiment, plasma levels of insulin and glucose and the systolic blood pressure of the two groups were continuously monitored for 17 days. In the subsequent four experiments, rats were killed on days 10 and 13 to measure plasma endothelin-1 (ET-1) levels and the glucose transport into and insulin and ET-1 binding of isolated adipocytes. In one experiment, rats were tested for oral glucose tolerance on days 10 and 13. In another experiment, ET-1 binding to the aortic plasma membrane was also determined. The results showed that rats became hyperinsulinemic throughout the experimental period by the instillation of exogenous insulin. Hyperinsulinemic rats were consistently hypoglycemic during the first day, but they became euglycemic thereafter, indicating an insulin-resistant state. Glucose intolerance was obvious by day 10, but significant hypertension was not detected until the 11th day on insulin infusion. Compared with the saline controls, insulin-infused rats had an increase of plasma ET-1 levels but a decrease of both basal and insulin-stimulated glucose transport into adipocytes. ET-1 binding to adipocytes of the insulin-infused group was elevated significantly from day 10 through day 13. ET-1 binding to the aortic membranes, supposedly downregulated by the increased plasma ET-1 and hypertension, was similar to that found in the controls on day 13. These results imply that hyperinsulinemia in rats could lead to hypertension via the elevation of plasma ET-1 levels together with an unaltered vascular binding of ET-1, which was probably unrelated to the insulin resistance.
- Published
- 1999
38. Evidence that endothelin-1 (ET-1) inhibits insulin-stimulated glucose uptake in rat adipocytes mainly through ETa receptors
- Author
-
Ching Fai Kwok, Low-Tone Ho, Shu Hsia Lin, Ying Chung Lee, Victor S. Fang, Yung Pei Hsu, and Chi Chang Juan
- Subjects
Male ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Glucose uptake ,Adipose tissue ,Peptide hormone ,Biology ,Binding, Competitive ,Rats, Sprague-Dawley ,Insulin Antagonists ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,Adipocyte ,Adipocytes ,medicine ,Animals ,Insulin ,RNA, Messenger ,Receptor ,Endothelin-2 ,Endothelin-3 ,Endothelin-1 ,Endothelins ,Endothelin 1 ,Peptide Fragments ,Rats ,Glucose ,chemistry ,Endothelin receptor ,Oligopeptides - Abstract
The specificity of endothelin (ET) receptors involved in the inhibition of insulin-stimulated glucose uptake (ISGU) in rat adipocytes was investigated. Adipocytes were isolated from the epididymal fat pads of Sprague-Dawley rats. To determine receptor subtypes, we used three ET isopeptides, ET-1 and ET-2, both of which are nonselective agonists, and ET-3, a selective agonist for ET c receptors, to displace [ 125 I]ET-1 binding from the fat cells. The efficiency of displacement was ET-1 > ET-2 ⪢ ET-3, indicating that the primary receptors involved belonged to the ET a subtype. At an equal concentration of 1 μmol/L, BQ-610, a selective ET a antagonist, displaced [ 125 I]ET-1 from binding to fat cells, whereas IRL-1038, a selective ET b antagonist, did not. Using [ 3 H]2-deoxy- d -1-glucose ([ 3 H]2-DG) as a tracer in studies of glucose uptake, we found that equimolar BQ-610 completely reversed the inhibitory effect of ET-1 on ISGU, whereas IRL-1038 was ineffective. Northern blot analysis of adipocyte receptors showed abundant mRNA for ET a , but no ET b subtype. These results clearly demonstrate that ET a is the predominant receptor in rat adipocytes.
- Published
- 1998
39. Steroid cell tumors of the ovary: clinical, ultrasonic, and MRI diagnosis—a case report
- Author
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Peng-Hui Wang, Hsiang-Tai Chao, Chiou-Chung Yuan, Heung-Tat Ng, Rheun-Chuan Lee, Ching-Fai Kwok, Wen-Ling Lee, and Chung-Ru Lai
- Subjects
Pathology ,medicine.medical_specialty ,Stromal cell ,Cell of origin ,Uterus ,Ovary ,Metastasis ,Humans ,Sex Cord-Gonadal Stromal Tumors ,Medicine ,Radiology, Nuclear Medicine and imaging ,Ovarian Steroid Cell Tumor ,Ovarian Neoplasms ,Leydig cell ,business.industry ,General Medicine ,Middle Aged ,Luteoma ,medicine.disease ,Magnetic Resonance Imaging ,Virilism ,medicine.anatomical_structure ,Uterine Neoplasms ,Female ,business - Abstract
Steroid cell tumors of the ovary are rare sex-cord neoplasms which account for less than 0.1% of all ovarian tumors. They have been divided into two subtypes according to their cell of origin as follows: stromal luteoma, and Leydig cell tumors, and a third subtype with lineage unknown is a steroid cell tumor, not otherwise specified (NOS). The clinical presentation may take many forms, including pain, abdominal distention and bloating, but perhaps the most interesting and noticeable presentations are those related to the hormonal activity and virilizing properties of the tumor. No radiological features of the steroid cell tumor, NOS have been presented in the literature. This report presents the MRI and ultrasonographic findings of a patient having steroid cell tumor, NOS, of the right ovary with metastasis to the uterus.
- Published
- 1998
40. Amelioration of insulin resistance and hypertension in a fructose-fed rat model with fish oil supplementation
- Author
-
Y.-C. Chou, Low-Tone Ho, Ching-Fai Kwok, Victor S. Fang, Chi Chang Juan, and Yan Jiun Huang
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Time Factors ,Normal diet ,Fasting hyperinsulinemia ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Glucose uptake ,Blood Pressure ,Fructose ,Biology ,Binding, Competitive ,Cohort Studies ,Iodine Radioisotopes ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Fish Oils ,Endocrinology ,Insulin resistance ,Internal medicine ,Adipocytes ,medicine ,Animals ,Insulin ,Dose-Response Relationship, Drug ,Endothelin-1 ,Body Weight ,Hypertriglyceridemia ,medicine.disease ,Fish oil ,Rats ,Disease Models, Animal ,Diabetes Mellitus, Type 2 ,chemistry ,Dietary Supplements ,Hypertension ,Insulin Resistance - Abstract
In type II diabetic patients, one can detect several pathologic changes including insulin resistance and hypertension. Sprague-Dawley rats fed a fructose-rich diet (group F) exhibited these characteristic abnormalities within 2 weeks and were an excellent laboratory animal model for research on insulin action and development of hypertension. Since fish oils containing omega-3 fatty acids have a beneficial effect in preventing atherosclerotic diseases, we performed repeated experiments to test the effects of fish oil supplementation in group F rats. Compared with control rats on a normal diet (group C), group F consistently developed hypertriglyceridemia without elevated plasma free fatty acid (FFA), fasting hyperinsulinemia together with fasting hyperglycemia (insulin resistance syndrome), and systolic hypertension within 3 weeks. Insulin-stimulated glucose uptake and insulin binding of adipocytes were significantly reduced. Rats fed the same high-fructose diet but supplemented with fish oil (group O) had alleviation of all of these metabolic defects and a normalized insulin sensitivity and blood pressure. beta-Cell function as shown by plasma glucose and insulin responses to oral glucose remained intact in group F and group O. The plasma endothelin-1 (ET-1) level and ET-1 binding to adipocytes were not different among the three groups. Based on these results, we suggest that dietary high fructose induced hypertriglyceridemia and insulin resistance with normal islet function, and that the induced hypertension was not associated with plasma ET-1 abnormalities and was probably caused by other undefined pathologic changes that can be prevented by dietary omega-3 fatty acids.
- Published
- 1997
41. Growth Hormone (GH) Replacement Reduces Total Body Fat and Normalizes Insulin Sensitivity in GH-Deficient Adults: A Report of One-Year Clinical Experience1
- Author
-
Kuang-Chung Shih, Sheng-Hung Lee, Low-Tone Ho, Chii-Min Hwu, Tian-Shing Lee, Li-Chuan Hsiao, Ching Fai Kwok, Tzong-Yoe Lai, and Victor S. Fang
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,Biochemistry (medical) ,Clinical Biochemistry ,Adipose tissue ,medicine.disease ,Biochemistry ,law.invention ,Endocrinology ,Insulin resistance ,Randomized controlled trial ,law ,Internal medicine ,Medicine ,Circadian rhythm ,business ,Homeostasis ,Pancreatic hormone ,Morning - Abstract
The effects of GH replacement on body fat composition and insulin sensitivity were assessed in GH-deficient adults. The patients were randomized into a double-blind, placebo-controlled study of human recombinant GH replacement therapy for 6 months (period 1), followed by an open phase of GH for another 6 months (period 2). Anthropometric variables, body fat composition (fat %), and biochemical parameters were measured during the trial. Measurements of in vivo insulin sensitivity were carried out at the commencement of the study and on completion of the trial by modified insulin suppression test. The modified insulin suppression test was performed both in the morning (AM) and in the afternoon (PM) to further evaluate the PM-AM steady-state plasma glucose (SSPG) pattern. We found that the GH-deficient adults had more body fat and were insulin resistant. Significant reduction in fat % and total body fat mass was found in the active arm of period 1 without alteration of body weight. Besides, we demonstrated, ...
- Published
- 1997
42. Acarbose plus metformin fixed-dose combination outperforms acarbose monotherapy for type 2 diabetes
- Author
-
Ching-Chu Chen, Ching-Ling Lin, Jun-Sing Wang, Ching-Fai Kwok, Chien-Ning Huang, Wayne Huey-Herng Sheu, Dee Pei, Yi-Jen Hung, Jui-Hung Sun, and Chwen-Yi Yang
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,endocrine system diseases ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Fixed-dose combination ,Type 2 diabetes ,Gastroenterology ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Significant risk ,Acarbose ,Aged ,Alpha-glucosidase inhibitor ,Glycated Hemoglobin ,business.industry ,Body Weight ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,medicine.disease ,Metformin ,Drug Combinations ,Postprandial ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Female ,business ,medicine.drug - Abstract
To compare the efficacy and safety of acarbose plus metformin fixed-dose combination (FDC) versus acarbose monotherapy for type 2 diabetes (T2D).Eligible T2D patients undergoing treatment with diet control only or oral antidiabetic medications were run-in on acarbose 50mg thrice-daily for 4 weeks, then randomised either to continue this monotherapy, or to acarbose 50mg plus metformin hydrochloride 500mg FDC (acarbose/metformin FDC), each thrice-daily for 16 weeks.Acarbose/metformin FDC therapy significantly reduced HbA1c, fasting plasma glucose (FPG), and postprandial plasma glucose (PPG) from baseline (all p0.0001) with superior efficacy compared with acarbose monotherapy (between-group differences; HbA1c -1.35%; FPG -29.5mg/dl; PPG -41.6mg/dl; all p0.0001). Proportionally more patients treated with acarbose/metformin FDC achieved HbA1c7.0% (47.8% vs. 10.7%, p0.0001). Both treatments reduced bodyweight (p0.0001), with a significant between-group difference (-0.6kg, p0.01) favouring acarbose/metformin FDC. Hypoglycaemia was not reported with either treatment, and the incidence of other adverse events did not differ significantly between the groups.Compared with acarbose monotherapy, acarbose/metformin FDC has superior antihyperglycaemic efficacy, brings proportionally more T2D patients to HbA1c goal, and further reduces bodyweight. Acarbose/metformin FDC is well-tolerated without significant risk of hypoglycaemia and is a potentially advantageous therapy for T2D.
- Published
- 2013
43. Effect of growth hormone on dawn phenomenon in patients with type 2 diabetes
- Author
-
Chii-Min Hwu, Kuang-Chung Shih, Low-Tone Ho, Sheng-Hwu Hsieh, Po-Shiuan Hsieh, and Ching-Fai Kwok
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Clinical Biochemistry ,Dawn phenomenon ,Octreotide ,Type 2 diabetes ,Endocrinology ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,business.industry ,Human Growth Hormone ,Insulin ,Drug Chronotherapy ,Cell Biology ,Glucose clamp technique ,medicine.disease ,Diabetes Mellitus, Type 2 ,Glucose Clamp Technique ,Female ,Insulin Resistance ,business ,Hormone ,medicine.drug - Abstract
We aimed to investigate the involvement of growth hormone in dawn phenomenon and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). On six occasions separated by intervals of at least 3 days, subjects received early evening (16:00 hours) or late night (23:00 hours) pretreatment with subcutaneous injection of normal saline, human growth hormone, or octreotide. Modified euglycemic insulin clamp test was done 16 hours later and variable glucose infusion (M values) was determined. Plasma glucose, serum insulin, insulin-like growth factor-1, non-esterified fatty acids, and metabolic clearance rate of insulin (MCRI) were measured. Early evening application of growth hormone decreased MCRI 16 hours later, suggesting reduction in insulin sensitivity. Exogenous growth hormone injection reduced insulin sensitivity in T2DM patients. Results provide direct evidence for the role of growth hormone in regulating the insulin sensitivity in insulin-resistant patients.
- Published
- 2013
44. Endothelin-1 Induces Insulin Resistance in Conscious Rats
- Author
-
Chi Chang Juan, Yung Pei Hsu, Victor S. Fang, Yan Jiun Huang, Ching Fai Kwok, and Low-Tone Ho
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Biophysics ,Carbohydrate metabolism ,Arginine ,Nitric Oxide ,Body weight ,Biochemistry ,Rats, Sprague-Dawley ,Insulin resistance ,Internal medicine ,medicine ,Pi ,Animals ,Insulin ,Insulin secretion ,Molecular Biology ,Saline ,Endothelin-1 ,Chemistry ,Cell Biology ,Glucose Tolerance Test ,medicine.disease ,Endothelin 1 ,Rats ,Endocrinology ,Insulin Resistance - Abstract
Since endothelin-1 (ET-1) might regulate insulin secretion and glucose metabolism, we carried out experiments to study the effect of ET-1 in conscious rats by injecting ET-1 (0.5 or 1.0 μg/100 g body weight, i.p.) and examining the plasma glucose (PG) and insulin (PI) concentrations and PG/PI ratios continuously for 3 hours after the injection. Compared to the saline controls, ET-1 increased PG and PG/PI ratios in a dose-dependent manner. Oral glucose tolerance test (OGTT) performed at 30 min after the injection showed that PG levels stayed significantly higher in rats preinjected with ET-1 than rats with saline injection, although the change in PI levels was not different. Simultaneous infusion of glucose and insulin to somatostatin-primed rats with ET-1 or saline injection resulted in significantly higher steady state plasma glucose (SSPG) levels and SSPG/PI ratios in rats injected with ET-1 than control rats with saline. These results unequivocally indicated that intraperitoneally administered ET-1 induces insulin resistance in conscious rats.
- Published
- 1996
45. Inertia on hypoglycemia: highlight from a Taiwan subgroup analysis of Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) study
- Author
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Shih-Te Tu, Kuang-Chung Shih, Chien-Wen Chou, Chih-Yuan Wang, Yu-Yao Huang, Ching-Ling Lin, Chen-Chung Fu, Rue-Tsuan Liu, Sheng-Hwu Hsieh, Huang Chien-Ning, Hing-Chung Lam, Tien-Shiang Huang, Ming-Nan Chien, Ta-Jen Wu, Ching-Fai Kwok, Chwen Tzuei Chang, and Wayne Huey-Herng Sheu
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Health Knowledge, Attitudes, Practice ,Asia ,Endocrinology, Diabetes and Metabolism ,Taiwan ,Subgroup analysis ,Type 2 diabetes ,Comorbidity ,Hypoglycemia ,Pacific Islands ,Risk Assessment ,Endocrinology ,Diabetes management ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Intensive care medicine ,Glycemic ,Quality of Health Care ,Glycated Hemoglobin ,business.industry ,Blood Glucose Self-Monitoring ,Type 2 Diabetes Mellitus ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Cross-Sectional Studies ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Patient Compliance ,Female ,business - Abstract
Type 2 diabetes mellitus is a global health issue. Patients with poor glycemic control often suffer from cardiovascular, cerebrovascular, neuropathic, and nephropathic complications as well as other chronic conditions. Therapeutic guidelines recommend that diabetic patients should maintain their HbA(1c) level below a certain target in order to minimize the risk of developing complications. However, hypoglycemia is recognized as a major impediment to the adequate control of type 2 diabetes. Hypoglycemia can manifest symptoms of varying degrees of severity. Moreover, an association between hypoglycemia and cardiovascular morbidity and mortality has been reported. Here, we present a post hoc Taiwan subgroup analysis of these data collected in the RECAP-DM study to indicate probably more emphasis and concern on hypoglycemia in type 2 diabetic patients in Taiwan. In this analysis, we found no significant difference was observed in treatment-related satisfaction between Taiwanese patients with or without hypoglycemia. Another finding of our study further shows that varying order of hypoglycemic symptoms or severity has no effect on patients' assessment of health-related quality of life scores. We need to pay more attention to this issue because of its enduring impact on compliance and concerns about hypoglycemia in type 2 diabetic patients. Nevertheless, socio-demographic characteristics are also important factors influencing glycemic control and patients' health-related quality of life. Future interventions and therapeutic algorithms should emphasize the probable patients' unawareness or neglect on hypoglycemia in diabetic patients.
- Published
- 2012
46. Resistin induces monocyte-endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression in endothelial cells via p38MAPK-dependent pathway
- Author
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Ying Lan Tsai, Ching Fai Kwok, Low-Tone Ho, Chih Chan Lien, Ming Chung Deng, Wei Yen Hsu, Chi Chang Juan, Chao Fu Chang, and Yu Wen Chao
- Subjects
medicine.medical_specialty ,endocrine system diseases ,Physiology ,Pyridines ,Clinical Biochemistry ,Vascular Cell Adhesion Molecule-1 ,Biology ,p38 Mitogen-Activated Protein Kinases ,Umbilical vein ,Monocytes ,Cell Line ,chemistry.chemical_compound ,Internal medicine ,medicine ,Cell Adhesion ,Humans ,Resistin ,VCAM-1 ,Enzyme Inhibitors ,Cell adhesion ,Cells, Cultured ,ICAM-1 ,Tumor Necrosis Factor-alpha ,Monocyte ,Imidazoles ,nutritional and metabolic diseases ,Endothelial Cells ,Cell Biology ,Adhesion ,respiratory system ,Intercellular Adhesion Molecule-1 ,Cell biology ,Endothelial stem cell ,Endocrinology ,medicine.anatomical_structure ,chemistry ,hormones, hormone substitutes, and hormone antagonists - Abstract
Resistin, firstly reported as an adipocyte-specific hormone, is suggested to be an important link between obesity and diabetes. Recent studies have suggested an association between resistin and atherogenic processes. The adhesion of circulating monocytes to endothelial cells is a critical step in the early stages of atherosclerosis. The purpose of the present study was to investigate the effect of resistin on the adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. Our results showed that resistin caused a significant increase in monocyte adhesion. In exploring the underlying mechanisms of resistin action, we found that resistin-induced monocyte adhesion was blocked by inhibition of p38MAPK activation using SB203580 and SB202190. Furthermore, resistin increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by HUVECs and these effects were also p38MAPK-dependent. Resistin-induced monocyte adhesion was also blocked by monoclonal antibodies against ICAM-1 and VCAM-1. Taken together, these results show that resistin increases both the expression of ICAM-1 and VCAM-1 by endothelial cells and monocyte adhesion to HUVECs via p38MAPK-dependent pathways.
- Published
- 2011
47. Insulin-like growth factor-I receptor increases in aortic endothelial cells from diabetic rats
- Author
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Jap Ts, Ching Fai Kwok, and Low-Tone Ho
- Subjects
medicine.medical_specialty ,Time Factors ,Endothelium ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,media_common.quotation_subject ,Binding, Competitive ,Receptor, IGF Type 1 ,Endocrinology ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Rats, Inbred BB ,Insulin-Like Growth Factor I ,Internalization ,Receptor ,Aorta ,Cells, Cultured ,media_common ,business.industry ,Growth factor ,Affinity Labels ,Protein-Tyrosine Kinases ,medicine.disease ,Rats ,Endothelial stem cell ,Disease Models, Animal ,Diabetes Mellitus, Type 1 ,medicine.anatomical_structure ,Cell culture ,Autoradiography ,Electrophoresis, Polyacrylamide Gel ,Endothelium, Vascular ,business ,Tyrosine kinase ,Diabetic Angiopathies - Abstract
Endothelial cells are likely to play an important role in the development of diabetic vascular diseases, since they are exposed directly to the abnormal circulating metabolites of diabetes and may be easily damaged early in the natural course of vascular complications. In this study, aortic endothelial cells were cultured from diabetic BB rats. Their binding and internalization of insulin-like growth factor-I (IGF-I) were measured. IGF-I binding was higher in cells of diabetic rats than of control rats at both 37 degrees C (4.5% +/- 1.6% v 2.74% +/- 0.9% per mg protein, P < .05) and 4 degrees C (20.6% +/- 5.6% v 13.7% +/- 4.6% per mg protein, P < .01). Internalization of IGF-I also increased (1.62% +/- 0.2% v 0.74% +/- 0.15% of total count at 37 degrees C after 60 minutes, P < .05). Cross-linking studies showed that in cells from diabetic rats, the major band of 140 kd corresponding to the alpha-subunit of the IGF-I receptor increased in density by 50% compared with those from control rats. The IGF-I-stimulated tyrosine kinase activity (TKA) of partially purified receptor from cells of diabetic rats, measured using poly-glu-tyr as substrate, was normal. Since the biological effects of IGF-I are initiated by its binding to the IGF-I receptor, which is able to transduce mitogenic and metabolic signals, our results support the hypothesis that the IGF-I receptor is involved in the development of diabetic vascular complications.
- Published
- 1993
48. Look Action for Health in Diabetes trial: What we have learned in terms of real world practice and clinical trials
- Author
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Ching-Fai Kwok and Low-Tone Ho
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,United Kingdom Prospective Diabetes Study ,General Medicine ,Type 2 diabetes ,Overweight ,medicine.disease ,Obesity ,law.invention ,Randomized controlled trial ,Weight loss ,law ,Diabetes mellitus ,Internal medicine ,Commentaries ,Internal Medicine ,medicine ,Physical therapy ,Prediabetes ,medicine.symptom ,business - Abstract
Type 2 diabetes is the most common form of diabetes, affecting more and more people all over the world. Complications of type 2 diabetes include heart disease, stroke, blindness, nephropathy, neuropathy and amputations. It has long been known that lifestyle intervention is beneficial for the prevention and treatment of type 2 diabetes. Short-term studies have shown that weight loss improves control of blood sugar, and mitigates risk factors for heart disease and stroke in overweight and obese individuals with type 2 diabetes. However, the longer-term effects of weight loss have not been well studied, and a critical question remains: would an intensive lifestyle intervention (ILI) to lose bodyweight through caloric restriction and increased physical activity decrease cardiovascular morbidity and mortality among overweight or obese adults with type 2 diabetes? Recently, the results of the Look Action for Health in Diabetes (AHEAD) trial, the largest landmark study aimed to fill the gap in existing data about whether ILI would decrease cardiovascular disease (CVD), came up with interesting findings. ILI was unable to reduce cardiovascular events and mortality1. Initiated in 2001, the trial enrolled more than 5,000 adults at 16 clinical centers across the USA. It is the longest intervention study of its type ever undertaken for diabetes. A total of 5,145 diabetic patients with body mass index (BMI) >25 were randomly assigned to either the ILI arm, in which patients were provided with individual sessions with a nutritionist, group sessions and refresher courses; or the diabetes support and education (DSE) arm, in which patients were given education and attended meetings twice a year, but they did not receive the intervention that was provided to the ILI group. The goal of the intervention was achieving and maintaining weight loss of at least 7%. The primary outcome of that study consisted of non-fatal myocardial infarction, non-fatal stroke, death or hospitalization for angina. After 11 years, the results showed no significant difference in the primary outcome between the two groups despite substantial reductions in bodyweight and improvements in many CVD risk factors, including treadmill fitness, blood pressure, high-density lipoprotein cholesterol and hemoglobin A1c1,2. Indeed, the trial concluded in 2012 after a median follow up of 9.6 years, when interim analyses suggested that it was very unlikely that further follow up would yield a different result. Why did weight loss fail to reduce the rate of CVD or mortality in this trial? There are several possible explanations. First, although the weight loss achieved in the ILI group was one of the best that has been achieved with current lifestyle approaches, it is not enough to reduce the rate of CVD, and sustained larger weight loss might be required. Second, the rate of cardiac events was lower than expected in both groups (DSE 1.92, ILI 1.83 events/100 person-years). In fact, the study investigators had to expand the definition of the study outcome so they would have enough events to measure1. Third, the increased use of statins in the DSE group might have lessened the difference in CVD rates between the two groups, probably by decreasing the blood levels of low-density lipoprotein cholesterol and C-reactive protein, both are risk factors for atherosclerosis progression and CVD. This notion is supported by the results showing that reductions in low-density lipoprotein cholesterol levels averaged across the first 4 years of the trial were greater in DSE than ILI participants (−12.84 vs −11.27 mg/dL; P = 0.009)2. In addition, the median C-reactive protein levels after 1 year of the trial were 2.6 mg/L for participants receiving statins in the DSE group and 2.9 mg/L for those randomized to ILI, but not receiving statins3. Fourth, as the 1-year and 4-year findings of the trial were already published and well publicized, the participants in the DSE group might have taken more action to lose weight and eat a healthy diet. Therefore, the CVD risks for all participants might have been reduced at a comparable rate. Fifth, it is also possible that ILI might cause a real reduction in CVD risks, but that it requires more than 10 years to become apparent. Indeed, the results of the United Kingdom Prospective Diabetes Study showed no difference in CVD at 12 years, but a significant difference at 20 years. Look AHEAD will now change into an observational cohort study in which patients will be followed over time and then the ‘legacy effect’ might become apparent later. Sixth, although weight loss and exercise can prevent diabetes in adults with prediabetes, once diabetes is established, they are not going to reduce the risk for macrovascular complications (Table(Table11). Table 1 Reasons to explain why weight loss failed to reduce the rate of cardiovascular disease and findings supporting health benefits in overweight diabetic patients in the Look Action for Health in Diabetes trial Patients with type 2 diabetes and overweight or obesity might ask whether they can stop exercising and go out to eat anything they wish. The answer is of course ‘no,’ because there is an overwhelming amount of evidence from this study and others that have shown that weight loss and physical activity were associated with numerous health benefits. For instance, nephropathy, which is a major factor associated with worse quality of life and higher mortality in diabetic patients, was 31% lower in the ILI group. Other benefits of weight loss and exercise include 14% decrease in eye disease, less obstructive sleep apnea, improved sexual dysfunction in women, fewer hospitalizations, less urinary incontinence and reduced medication use1. All these continue to be reasons to recommend overweight diabetic patients to adopt a healthy lifestyle. Finally, how about diet composition? The achieved dietary changes are not reported in the Look AHEAD trial. The role of dietary composition is not completely clear. Interest in the possible benefits of a Mediterranean-style diet rich in monounsaturated and polyunsaturated fat and lower in saturated fat started in the 1950s, and was boosted in 1994 when a large French trial found that it reduced mortality in patients after myocardial infarction. Since then, a persuasive body of evidence from observational studies has documented that Mediterranean-style diets are associated with a substantially reduced risk of CVD. Furthermore, the adoption of the Mediterranean diet has been associated with a significant reduction in new cancers. Recently, the results of a large randomized controlled trial extended the findings to persons at high risk for CVD4. Thus, the Mediterranean diet pattern can be considered an effective approach for the prevention of fatal and non-fatal CVD complications. This diet pattern is rich in monounsaturated fat, polyphenols and polyunsaturated fat, including alpha-linolenic acid. Further studies are warranted to examine in more detail what the important components are and how they work. Another issue worth mentioning is fructose. Fructose is a major component of added sugars. In the last 100 years, intake of fructose has increased dramatically, and correlates closely with the rise in obesity, metabolic syndrome and diabetes. Fructose is distinct from other sugars in its ability to cause intracellular adenosine triphosphate depletion, nucleotide turnover and the generation of uric acid. The discovery provides new insights into the pathogenesis and therapies for this important disease5. Furthermore, a low-fat diet, as adopted in this trial, might be accompanied by increasing the portion size of carbohydrate intake to be isocaloric in the ILI group, which might contribute a confounding factor in dietary impacts. In conclusion, although intensive lifestyle therapy did not decrease the rate of CVD in the Look AHEAD trial, it is reasonable to recommend overweight people to increase physical activity, eat healthily and to lose weight. The earlier this is done the better. Furthermore, the possible benefits of individual food components require further investigation. Lifestyle therapy might have to focus not only on bodyweight, but also on diet composition. As for evidence on beneficial CVD outcomes, mega-trials with stratified control in confounding factors, especially ‘cardioprotective’ drugs, remain to be seen.
- Published
- 2014
49. Clinical observations, molecular genetic analysis, and treatment of sitosterolemia in infants and children
- Author
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Dau Ming Niu, Hsiao Chi Yu, Tina Jui Ting Wu, Kah Wai Chong, Ju Hui Hsu, Ming Yu Lo, Lisa E. Kratz, Low Tone Ho, Cheng Hung Huang, and Ching Fai Kwok
- Subjects
medicine.medical_specialty ,Pediatrics ,Lipoproteins ,DNA Mutational Analysis ,Older patients ,Ezetimibe ,Asian People ,Internal medicine ,Genetics ,medicine ,Humans ,Point Mutation ,Genetic Testing ,ATP Binding Cassette Transporter, Subfamily G, Member 5 ,Child ,Genetics (clinical) ,Genetic testing ,Cholestyramine ,medicine.diagnostic_test ,business.industry ,Anticholesteremic Agents ,Genetic observations ,Infant ,medicine.disease ,Sitosterols ,Molecular analysis ,Endocrinology ,El Niño ,Azetidines ,ATP-Binding Cassette Transporters ,Female ,business ,Sitosterolemia ,Metabolism, Inborn Errors ,medicine.drug - Abstract
The clinical observation and treatment of young children with sitosterolemia has rarely been reported. We report clinical, biochemical, and molecular genetic observations and treatment outcomes for five Chinese children from four separate families presenting with sitosterolemia in whom we identified two new (Y329X, G269R) and three known (R446X, N437K, R389H) mutations in the ABCG5 gene. The R389H mutation was found in 50% of alleles. Three of these five patients received cholestyramine therapy with a very good response. However, all patients discontinued this therapy because of poor compliance. Finally, all patients were on ezetimibe therapy and had satisfactory total serum cholesterol levels, though their plant sterol levels were still higher than normal. Another noteworthy finding is that a female infant had a serum cholesterol level of 654 mg/dl at 7 months of age, despite being breast fed (with very tiny amounts of plant sterols) since birth and undergoing 4 months of ezetimibe administration. Although she failed to respond to ezetimibe during this period, she did show improvement when the therapy was started again at 2 years of age. It is possible that another 23-month-old female patient also responded more slowly to ezetimibe treatment than older patients.
- Published
- 2009
50. Effects of exercise on insulin sensitivity, inflammatory cytokines, and serum tartrate-resistant acid phosphatase 5a in obese Chinese male adolescents
- Author
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Kuang Chung Shih, Tsu Yi Chao, Anthony J. Janckila, Yu-Ching Chou, Low-Tone Ho, and Ching Fai Kwok
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Acid Phosphatase ,Physical exercise ,Body Mass Index ,Endocrinology ,Insulin resistance ,Internal medicine ,medicine ,Humans ,Insulin ,Obesity ,Exercise ,Pancreatic hormone ,Glucose tolerance test ,medicine.diagnostic_test ,biology ,business.industry ,Tartrate-Resistant Acid Phosphatase ,C-reactive protein ,Glucose Tolerance Test ,medicine.disease ,Isoenzymes ,biology.protein ,Cytokines ,Inflammation Mediators ,Insulin Resistance ,business ,Body mass index - Abstract
The benefits of exercise on glucose metabolism, inflammation, and serum tartrate-resistant acid phosphatase 5a (TRACP 5a) protein levels in Chinese male adolescents have not been extensively analyzed. Therefore, we examined the effects of a 12-week exercise program on weight, adiposity, insulin sensitivity (IS), and inflammatory marker expression, including the novel macrophage marker TRACP 5a, in obese Chinese male adolescents. A total of 106 male adolescents were recruited from the Army Academy in Taiwan and classified as lean (body mass index [BMI], 20.9 +/- 0.2 kg/m(2)) or obese (BMI, 27.7 +/- 0.2 kg/m(2)). Body composition, IS, and inflammatory markers were measured in both groups at baseline and in the obese group after completion of a 12-week exercise program. Body weight, BMI, waist circumference, body fat mass and percentage, homeostasis model assessment for insulin resistance, fasting plasma glucose, fasting serum insulin, 2-hour postchallenge plasma glucose concentration, interleukin-6, C-reactive protein, and serum TRACP 5a were significantly higher in the obese group as compared with the lean group. In addition, serum TRACP 5a was positively correlated with body mass and fat indices. After completion of the exercise program, significant reductions in all anthropometric, metabolic, and inflammatory indicators, with the exception of serum TRACP 5a were observed. Although the obese participants remained obese, exercise training significantly improved IS and reduced interleukin-6 and C-reactive protein. Tartrate-resistant acid phosphatase 5a remained unaffected by exercise training, consistent with our hypothesis that it is associated with increased adipose tissue in obese individuals.
- Published
- 2008
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