27 results on '"Motoyoshi Ikebuchi"'
Search Results
2. Effects of hyperglycemia on oxidative stress and antioxidant potential in patients with type 2 diabetes
- Author
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Motoyoshi Ikebuchi, Hiroshi Maegawa, Atsunori Kashiwagi, and Yoshihiko Nishio
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Miglitol ,Type 2 Diabetes Mellitus ,Type 2 diabetes ,medicine.disease ,medicine.disease_cause ,Glimepiride ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Metabolic syndrome ,business ,Oxidative stress ,Glycemic ,medicine.drug - Abstract
Many in vitro studies have suggested that oxidative stress induced by hyperglycemic conditions has a pivotal role in the pathogenesis of vascular complications in diabetics. This study intended to evaluate the oxidative stress and antioxidant potential in patients with type 2 diabetes mellitus (DM), and to clarify the relation between oxidative stress and metabolic derangements including chronic hyperglycemia. We measured the levels of derivatives of reactive oxidative metabolites (ROM) and biological antioxidant potential (BAP) in 59 patients with type 2 DM and 10 healthy controls. Diabetic patients showed a significant increase in ROM levels and a decrease in adjusted BAP/ROM ratios compared with those of control. But no differences were found in BAP levels between the two groups. ROM levels were found to positively correlate with HbA1c, plasma glucose, and waist size, and adjusted BAP/ROM ratios negatively correlated with HbA1c, plasma glucose, waist size, and serum triglycerides. Stepwise multiple regression analysis indicated that HbA1c and waist size were independent factors contributing to the elevated ROM levels. The ROM level in patients with type 2 DM with metabolic syndrome was significantly higher than that in patients without metabolic syndrome. Glycemic control with glimepiride or miglitol for 3 months reduced ROM levels significantly by 9%. These results clearly demonstrate that glycemic control and visceral obesity are independently associated with an increasing oxidative stress in patients with type 2 DM.
- Published
- 2010
3. Effect of Bezafibrate Treatment on the Altered Lipoprotein Profiles in Hypertriglyceridemic Subjects
- Author
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Masaaki Suzuki, Yutaka Harano, Mihoko Norioka, Kayoko Ryomoto, and Motoyoshi Ikebuchi
- Subjects
medicine.medical_specialty ,Very low-density lipoprotein ,Apolipoprotein B ,Lipoproteins ,Cholesterol, VLDL ,Lipoproteins, VLDL ,Hyperlipoproteinemia Type IV ,digestive system ,chemistry.chemical_compound ,Internal medicine ,polycyclic compounds ,Internal Medicine ,medicine ,Humans ,Lipoprotein metabolism ,Triglycerides ,Apolipoproteins B ,Hypolipidemic Agents ,Hypertriglyceridemia ,Acid derivative ,Bezafibrate ,Triglyceride ,biology ,Biochemistry (medical) ,technology, industry, and agriculture ,nutritional and metabolic diseases ,Plasma levels ,Cholesterol ,Endocrinology ,chemistry ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine ,Lipoprotein ,medicine.drug - Abstract
The effects of bezafibrate treatment on lipoprotein metabolism were investigated in hypertriglyceridemic subjects. Bezafibrate, a fibric acid derivative, was administered at 200-400 mg/day to 8 patients with hyperlipoproteinemia (type IIb and IV) for 3-6 months. We evaluated the effects of bezafibrate on the plasma levels of total cholesterol(chol), triglyceride(TG), and apoB. In addition, the lipid and apoB contents were also analyzed in VLDL, IDL, LDL and HDL fractions before and after the treatment. It was revealed that plasma levels of chol, TG and apoB significantly decreased after the treatment, 236.3 vs 210.9,192.4 vs 90.2 (p< 0.01) and 129.8 vs 116.2 (p
- Published
- 2000
4. Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose uptake in non-insulin-dependent diabetes mellitus
- Author
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Kentaro Mochizuki, Yoshimitsu Yamasaki, Masahiko Ikeda, Ryohei Tohdo, Masahiko Wada, Masataka Niwa, Ryuzo Kawamori, Tsutomu Kanda, Tomoyuki Arisaka, Junichiro Kinoshita, Munehide Matsuhisa, Motoyoshi Ikebuchi, and Minoru Kubota
- Subjects
Glucose tolerance test ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,Glucose uptake ,General Medicine ,Glucose clamp technique ,medicine.disease ,Sulfonylurea ,Endocrinology ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,Medicine ,business ,Pioglitazone ,medicine.drug - Abstract
To evaluate the effect of pioglitazone on insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) patients, a double-blind placebo-controlled trial was carried out with 30 NIDDM patients. Twenty-one subjects, three on diet alone and 18 on sulfonylurea (SU), orally received 30 mg pioglitazone once daily for 12 weeks. Nine subjects, one on diet alone and eight on SU, received a matching placebo once daily for 12 weeks. Euglycemic (5.2 mmol/l) hyperinsulinemic (1200 pmol/l) clamp combined with an oral glucose load (OGL) was performed before and after 3-month treatment with pioglitazone or placebo to determine insulin-stimulated glucose disposal and splanchnic glucose uptake (SGU). No significant differences existed in the patients' characteristics, including age and body mass index, between the two study groups. The pioglitazone treatment increased the mean glucose infusion rate (GIR) prior to OGL from 8.2 +/- 2.2 to 9.2 +/- 2.0 mg/kg.min (mean +/- SD, P = 0.003) and increased the SGU rate from 28.5 +/- 19.4 to 59.4 +/- 27.1% (P = 0.010). The placebo treatment produced no significant changes in either GIR or SGU after treatment. A significant difference (P = 0.042) was observed in change of SGU between the pioglitazone and placebo treatment groups. In conclusion, the results indicate that pioglitazone is effective for ameliorating insulin resistance in NIDDM by enhancing SGU as well as peripheral glucose uptake.
- Published
- 1998
5. Pyruvate improves deleterious effects of high glucose on activation of pentose phosphate pathway and glutathione redox cycle in endothelial cells
- Author
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Toshiyuki Obata, Noriko Takahara, Atsunori Kashiwagi, Hideki Hidaka, Ryuichi Kikkawa, Natsuki Harada, Takayuki Asahina, Motoyoshi Ikebuchi, Yasushi Tanaka, Hideki Taki, Yoshihiko Nishio, and Yukikazu Saeki
- Subjects
medicine.medical_specialty ,Umbilical Veins ,Endocrinology, Diabetes and Metabolism ,Pentose phosphate pathway ,Biology ,medicine.disease_cause ,Umbilical vein ,Pentose Phosphate Pathway ,chemistry.chemical_compound ,Adenosine Triphosphate ,Diabetes mellitus ,Internal medicine ,Pyruvic Acid ,medicine ,Fructosediphosphates ,Internal Medicine ,Humans ,Lactic Acid ,Cells, Cultured ,Glutathione ,Hydrogen Peroxide ,medicine.disease ,NAD ,In vitro ,Endothelial stem cell ,Endocrinology ,Glucose ,L-Glucose ,chemistry ,Endothelium, Vascular ,Oxidation-Reduction ,Oxidative stress ,NADP - Abstract
In our previous study (Diabetes 44:520–526, 1995), endothelial cells cultured in high glucose condition showed impairment of an oxidant-induced activation of the pentose phosphate pathway (PPP) and a reduced supply of NADPH to the glutathione redox cycle. To gain insight into the mechanisms of this impairment, the protective effect of pyruvate was studied in human umbilical vein endothelial cells cultured in either 5.5 mmol/l glucose (normal glucose [NG] condition) or 33 mmol/l glucose (high glucose [HG] condition). Through pretreatment of cells with 0.2 mmol/l pyruvate for 5–7 days in the HG condition, glucose oxidation through the PPP and total cellular NADPH content in the presence of 0.2 mmol/l H2O2 were increased by 54 (P < 0.05) and 34%, respectively, and glutathione-dependent degradation of H2O2 in HG cells was enhanced by 41% (P < 0.01), when compared with those cells to which pyruvate was not added. The addition of pyruvate significantly reduced the fructose 1,6-bisphosphate (FDP) content and free cytoplasmic NADH/NAD ratio, estimated by increased pyruvate/lactate ratio in NG and HG cells exposed to H2O2. Furthermore, the addition of pyruvate also showed a 46% reduction (P < 0.01) of endothelial cell damage induced by H2O2 in HG cells. These results indicate that abnormalities in PPP activation and glutathione redox cycle activity induced by H2O2 in HG cells are compensated, and that the accentuated reductive stress is improved by an addition of pyruvate. These pyruvate effects are associated with protection against an oxidant-induced endothelial cell injury in the high glucose condition.
- Published
- 1997
6. Lipoprotein analyses in patients with stable angina and acute coronary syndrome
- Author
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Motoyoshi Ikebuchi, Chiaki Yokota, Hiroshi Nonogi, Kazuya Shinozaki, Shunichi Miyazaki, Yoichi Goto, Masaaki Suzuki, Kazuo Haze, Yutaka Harano, and Yasushi Hara
- Subjects
Male ,medicine.medical_specialty ,Acute coronary syndrome ,Apolipoprotein B ,Myocardial Infarction ,Coronary Disease ,Lipoproteins, VLDL ,Angina Pectoris ,Coronary artery disease ,Electrocardiography ,chemistry.chemical_compound ,Risk Factors ,Internal medicine ,medicine ,Humans ,Angina, Unstable ,Myocardial infarction ,Aged ,Analysis of Variance ,medicine.diagnostic_test ,biology ,Cholesterol ,Unstable angina ,business.industry ,Middle Aged ,medicine.disease ,Lipoproteins, LDL ,Diabetes Mellitus, Type 2 ,chemistry ,biology.protein ,Cardiology ,Female ,lipids (amino acids, peptides, and proteins) ,Lipoproteins, HDL ,Cardiology and Cardiovascular Medicine ,Lipid profile ,business ,Lipoprotein - Abstract
We have performed lipid analyses by using a table-top ultracentrifuge based on the Hatch and Lees' method in 77 subjects (60 men, 17 women; mean age, 63 years) to clarify lipoprotein disorders in coronary artery disease. Sixty-four subjects had coronary artery disease and 13 normal subjects were controls. They were divided into the groups with stable angina pectoris and with unstable angina pectoris or acute myocardial infarction (acute coronary syndromes). In patients with coronary artery disease, there were no significant differences from control in age, body mass index, total cholesterol, however, HDL cholesterol was significantly lower than those in the controls. LDL cholesterol:LDL apoB ratio, which is thought to reflect the size of LDL in coronary artery disease, was significantly smaller than that in the controls; mean values were 1.2 in coronary artery disease and 1.4 in controls. There were no significant differences in those lipoprotein disorders between the patients with stable angina and those with acute coronary syndromes. Though these lipoprotein abnormalities would not play a trigger role in acute coronary syndromes, they are characteristic of the lipid profile of patients with coronary artery disease.
- Published
- 1996
7. Quantitative and Qualitative Derangement of Apolipoprotein B-Containing Lipoproteins as a Risk Factor for Diabetic Macroangiopathy in Nonobese NIDDM Subjects
- Author
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Kazuya Shinozaki, Yasuhiko Nakao, Motoo Tsushima, Aritsune Kageyama, Motoyoshi Ikebuchi, Masaaki Suzuki, Akira Sato, Yasushi Hara, and Yutaka Harano
- Subjects
Adult ,Male ,medicine.medical_specialty ,Very low-density lipoprotein ,Apolipoprotein B ,Lipoproteins ,Endocrinology, Diabetes and Metabolism ,Coronary Disease ,Coronary artery disease ,chemistry.chemical_compound ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Humans ,Medicine ,Obesity ,cardiovascular diseases ,Triglycerides ,Aged ,Apolipoproteins B ,biology ,Triglyceride ,business.industry ,Cholesterol ,Unstable angina ,nutritional and metabolic diseases ,Arteriosclerosis Obliterans ,Middle Aged ,medicine.disease ,Endocrinology ,Diabetes Mellitus, Type 2 ,chemistry ,biology.protein ,Female ,lipids (amino acids, peptides, and proteins) ,business ,Diabetic Angiopathies ,Lipoprotein - Abstract
Cholesterol, triglylceride (TG), and apolipoprotein (apo) B were determined in plasma and in lipoprotein subtractions (VLDL, intermediate-density lipoproteine [IDL], LDL, and HDL) in nonobese NIDDM subjects, who were classified into well-controlled, fairly controlled, or poorly controlled states with or without macrovascular complications (macroangiopathy [MA]). The same analyses were also performed on subjects who had coronary artery disease (CAD) with stable angina pectoris (SA) or unstable angina pectoris (UA) and acute myocardial infarction, cerebrovascular disease (CVD) with atherothrombotic or lacunar infarction, and arteriosclerosis obliterane (ASO). In nonobese NIDDM subjects, the number of apoB-con-taining lipoproteins (VLDL, IDL, and LDL) increased. This alteration was more prominent in subjects with poorly or fairly controlled disease as well as in subjects with MA, but not in those with well-controlled NIDDM. Cholesterol/apoB in LDL decreased in subjects with poorly and fairly controlled diabetes or with MA and was correlated with low HDL cholesterol. The disorder is characterized by hyperbetalipoproteinemia with elevated LDL cholesterol and small dense LDL. In obese NIDDM subjects, the similar disorder was more pronounced. Glycemic control had less effect and hyperinsulinemia, if present, aggravated the lipid disorder. In those with CAD, the number of IDLs increased and the LDL fraction had the properties of small dense LDL. HDL cholesterol decreased. In those with UA, the LDL number increased without elevation of LDL cholesterol, indicating typical hyperbetalipoproteinemia. In subjects with atherothrombotic brain infarction, an increased number of small-sized LDLs was noted. In those with ASO, the number of VLDL and IDL increased with small LDL. HDL cholesterol decreased in those with CAD, cerebrovascular disease, and ASO. Since similar quantitative and qualitative alterations of apoB-containing lipoprotein have been observed in NIDDM patients as well as in those with macrovascular diseases, diabetic patients are thought to be more susceptible to the initiation and progression of atheromatous lesions in coronary, brain, and peripheral arteries.
- Published
- 1996
8. Insulin Resistance Associated With Compensatory Hyperinsulinemia as an Independent Risk Factor for Vasospastic Angina
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Kazuya Shinozaki, Masaaki Suzuki, Motoo Tsushima, Hiroshi Takaki, Motoyoshi Ikebuchi, Yutaka Harano, and Yasushi Hara
- Subjects
Angina Pectoris, Variant ,Male ,Chest Pain ,medicine.medical_specialty ,medicine.medical_treatment ,Coronary Disease ,Coronary Angiography ,Impaired glucose tolerance ,Coronary artery disease ,Insulin resistance ,Risk Factors ,Hyperinsulinism ,Physiology (medical) ,Internal medicine ,medicine ,Hyperinsulinemia ,Humans ,Insulin ,Coronary atherosclerosis ,Glucose tolerance test ,medicine.diagnostic_test ,business.industry ,Discriminant Analysis ,Glucose Tolerance Test ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,Lipids ,respiratory tract diseases ,Endocrinology ,Case-Control Studies ,Cardiology ,Female ,Insulin Resistance ,Cardiology and Cardiovascular Medicine ,business ,Compensatory Hyperinsulinemia - Abstract
Background It is generally believed that coronary artery spasm plays an important role in the progression of obstructive coronary artery disease. Since insulin resistance together with hyperinsulinemia plays an important role in the pathogenesis of coronary atherosclerosis, we investigated the association of hyperinsulinemia and insulin resistance with vasospastic angina (VAP). Methods and Results The study population consisted of 60 patients with VAP and 42 control subjects (62 subjects with normal glucose tolerance and 40 with impaired glucose tolerance). Insulin sensitivity was determined by the steady-state plasma glucose (SSPG) method for nondiabetic, normotensive, nonobese subjects (16 control subjects, 16 obstructive coronary artery disease patients, and 16 VAP patients). Compared with the control groups, the 2-hour insulin area (area under the plasma insulin concentration-time curve) during a 75-g oral glucose tolerance test was significantly higher in both VAP groups with normal and impaired glucose tolerance. A high frequency of vasospastic angina was observed in subjects with clustered risk factors for insulin resistance syndrome, suggesting a close association of VAP with this syndrome. In stepwise discriminant analysis, the 2-hour insulin area was significantly associated with VAP independent of other risk factors. SSPG level in VAP was about twofold over control, indicating the presence of insulin resistance in patients with VAP. However, no differences were found between patients with VAP and obstructive coronary artery disease with respect to mean SSPG level. Conclusions SSPG level was significantly elevated in patients with VAP and obstructive coronary artery disease compared with control subjects. This indicates that hyperinsulinemia is secondary to insulin resistance, both of which are thought to play important roles as risk factors for VAP in the early atheromatous lesion and in the future development of occlusive lesions when chronically present.
- Published
- 1995
9. Impaired activation of glucose oxidation and NADPH supply in human endothelial cells exposed to H2O2 in high-glucose medium
- Author
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Ryuichi Kikkawa, Yoshihiko Nishio, Yukio Shigeta, Atsunori Kashiwagi, Yasushi Tanaka, Yoshihumi Takagi, Takayuk Asahina, Motoyoshi Ikebuchi, Yukikazu Saeki, and Natsuki Harada
- Subjects
Intracellular Fluid ,Phosphofructokinase-1 ,Endocrinology, Diabetes and Metabolism ,Glucose-6-Phosphate ,Glucosephosphate Dehydrogenase ,Pentose phosphate pathway ,medicine.disease_cause ,Pentose Phosphate Pathway ,chemistry.chemical_compound ,Adenosine Triphosphate ,medicine ,Internal Medicine ,Humans ,Glycolysis ,Lactic Acid ,Hydrogen peroxide ,Cells, Cultured ,Chemistry ,Glucosephosphates ,Glyceraldehyde-3-Phosphate Dehydrogenases ,Hydrogen Peroxide ,Glutathione ,NAD ,Phosphofructokinase activity ,Culture Media ,Endothelial stem cell ,Oxidative Stress ,Glucose ,Biochemistry ,Lactates ,Endothelium, Vascular ,NAD+ kinase ,Oxidation-Reduction ,Diabetic Angiopathies ,NADP ,Oxidative stress - Abstract
The effects of glucose concentration on D-glucose oxidation and reduced nicotinamide adenine dinucleotide phosphate (NADPH) supply were studied during exposure of cultured human umbilical vein endothelial cells to hydrogen peroxide (H2O2). The activation of glucose oxidation via the pentose phosphate pathway (PPP), induced by exposure of cells to 200 μmol/l H2O2 for 1 h, was reduced by 50% (P < 0.01) in cells cultured for 5–7 days in 33 mmol/l D-glucose (HG) versus those cultured in 5.5 mmol/l D-glucose without (NG) or with (HR) 27.5 mmol/l D-raffinose. The intracellular NADPH content in HG cells, but not in NG or HR cells, was decreased by 42% (P < 0.01) by exposing cells to 200 μmol/l H2O2. The decrease in NADPH was dependent on D-glucose concentration in the medium and was prevented in glutathione (GSH)-depleted cells. The latter observation suggests that the decrease in NADPH is associated with activation of the GSH redox cycle. In the presence of 200 μmol/l H2O2, lactate release into the medium, NADH/NAD ratio, and phosphofructokinase activity in HG cells were 56, 53, and 68% greater, respectively, than in the NG group, which indicates that inhibition of glycolysis by H2O2 is less marked in the HG group compared with NG group. These results indicate that activation of the PPP was impaired in endothelial cells cultured under conditions of high-glucose and oxidative stress, resulting in a decreased supply of NADPH to various NADPH-dependent pathways, including the GSH redox cycle.
- Published
- 1995
10. Improvement of insulin sensitivity for glucose metabolism with the long-acting Ca-channel blocker amlodipine in essential hypertensive subjects
- Author
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A. Kageyama, Yutaka Harano, J. Hirose, M. Suzuki, T. Omae, Y. Asakura, T. Yokota, and Motoyoshi Ikebuchi
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Natriuresis ,Ketone Bodies ,Carbohydrate metabolism ,Essential hypertension ,Catecholamines ,Endocrinology ,Insulin resistance ,Internal medicine ,medicine ,Homeostasis ,Humans ,Insulin ,Amlodipine ,Pancreatic hormone ,Glucose tolerance test ,medicine.diagnostic_test ,business.industry ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Lipids ,Hypertension ,Ketone bodies ,Female ,Insulin Resistance ,business ,medicine.drug - Abstract
To clarify whether the long-acting calcium-channel blocker amlodipine restores insulin insensitivity in essential hypertension, insulin sensitivity tests were performed at the physiological steady-state insulin level (45 to 55 microU/mL) before and after amlodipine (2.5 to 7.5 mg/d) administration for 2 to 4 months in borderline and mild essential hypertensive subjects. Instead of somatostatin, Sandostatin (Sandoz, Basel, Switzerland) was used for the determination of steady-state plasma glucose (SSPG) in the same way as previously described. SSPG, which was initially high (212.9 +/- 18.0 mg/dL, mean +/- SE), was significantly reduced to 169.8 +/- 14.7 after amlodipine treatment. Responses of ketone bodies during the test at 30 minutes, which reflect the insulin effect on lipolysis in adipose tissue and hepatic fatty acid oxidation, also improved after amlodipine treatment. Norepinephrine, noted to be mildly elevated after amlodipine treatment, decreased during the sensitivity test at 2 hours probably due to the sedative effect, without any change in the fractional extraction of Na. This indicates that the physiological level of insulin does not activate sympathetic nerve activity or stimulate Na reabsorption. The long-acting calcium-channel blocker amlodipine has significantly improved the initially decreased insulin sensitivity for glucose metabolism at least partially in borderline or mild essential hypertension.
- Published
- 1995
11. Abnormal glutathione metabolism and increased cytotoxicity caused by H2O2 in human umbilical vein endothelial cells cultured in high glucose medium
- Author
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Yoshihumi Takagi, Yukio Shigeta, Atsunori Kashiwagi, Yoshihiko Nishio, Ryuichi Kikkawa, Takayuki Asahina, Motoyoshi Ikebuchi, and Yuki Tanaka
- Subjects
Umbilical Veins ,medicine.medical_specialty ,Endothelium ,Endocrinology, Diabetes and Metabolism ,Biology ,medicine.disease_cause ,Umbilical vein ,chemistry.chemical_compound ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Cytotoxicity ,Cells, Cultured ,Glutathione Peroxidase ,Cell Death ,Free Radical Scavengers ,Hydrogen Peroxide ,Glutathione ,Metabolism ,NAD ,Culture Media ,Endothelial stem cell ,Glucose ,Glutathione Reductase ,Endocrinology ,medicine.anatomical_structure ,Biochemistry ,chemistry ,Endothelium, Vascular ,Oxidation-Reduction ,NADP ,Intracellular ,Oxidative stress - Abstract
To determine whether increased oxidative stress in diabetes mellitus is due to an impaired freeradical scavenger function in endothelial cells, GSH-dependent H2O2 degradation in human umbilical vein endothelial cells was studied. The GSH-dependent, NaN3-uninhibitable H2O2-degradation in endothelial cells was reduced by 48% (p
- Published
- 1994
12. Effect of medium pH on glutathione redox cycle in cultured human umbilical vein endothelial cells
- Author
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Yukio Shigeta, Takayuki Asahina, Ryuichi Kikkawa, Yoshihiko Nishio, Yasushi Tanaka, Motoyoshi Ikebuchi, Yoshihumi Takagi, Atsunori Kashiwagi, and Hideki Hidaka
- Subjects
Umbilical Veins ,medicine.medical_specialty ,Antioxidant ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Glutathione reductase ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,medicine ,Humans ,Hydrogen peroxide ,Cells, Cultured ,chemistry.chemical_classification ,Glutathione Disulfide ,Glutathione peroxidase ,Hydrogen Peroxide ,Intracellular Membranes ,Metabolism ,Glutathione ,Hydrogen-Ion Concentration ,Culture Media ,chemistry ,Glutathione disulfide ,Endothelium, Vascular ,Acids ,Oxidation-Reduction ,Intracellular - Abstract
Impairments of the glutathione redox cycle in cultured endothelial cells under acidic pH conditions were measured. Glutathione-dependent H2O2-degrading activities decreased by 20% (P < .01) at pH 6 and by 51% (P < .01) at pH 4 compared with activities at pH 7.4 1 hour after a change with fresh medium. Intracellular reduced glutathione (GSH) content increased by 85% (P < .01) following the change with pH 7.4 medium. Such increases in GSH content were impaired after exposure to acidic medium. After exposure to 500 mumol/LH2O2, intracellular GSH content decreased by 61% compared with the level obtained in the absence of H2O2 at pH 7.4 (P < .01). Compared with the level at pH 7.4, the H2O2-induced decrease in intracellular GSH content was 32% lower (P < .01) at pH 6 and did not change at all at pH 4. After exposure to 500 mumol/L H2O2, the intracellular oxidized glutathione (GSSG) content increased by 160% at pH 7.4 (P < .01), 370% at pH 6 (P < .01), and 90% at pH 4 compared with treatment without H2O2, respectively. After exposure to 500 mumol/L H2O2, the release of GSSG from cells at pH 6 decreased by 38% compared with the value found at pH 7.4 (P < .05), and the release at pH 4 completely disappeared. Both glutathione peroxidase (GPO) and glutathione reductase activities decreased as a function of a decrease in pH from 7.4 to 4.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
13. Effect of the pH of the Medium on Glutathione Redox Cycle in Cultured Endothelial Cells
- Author
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Atsunori Kashiwagi, Motoyoshi Ikebuchi, and Yukio Shigeta
- Subjects
chemistry.chemical_compound ,Biochemistry ,Chemistry ,Redox cycle ,Glutathione - Published
- 1992
14. Hyperbetalipoproteinemia with small low-density lipoprotein, a characteristic disorder of lipoprotein in essential hypertension
- Author
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Motoo Tsushima, Motoyoshi Ikebuchi, Masaaki Suzuki, Kayoko Ikeda, Akira Yamamoto, Yutaka Harano, and Yasushi Hara
- Subjects
Male ,medicine.medical_specialty ,Very low-density lipoprotein ,Apolipoprotein B ,Lipoproteins ,Endocrinology, Diabetes and Metabolism ,Lipoproteins, VLDL ,Essential hypertension ,Sensitivity and Specificity ,Body Mass Index ,Cohort Studies ,Hyperlipoproteinemia Type II ,chemistry.chemical_compound ,Endocrinology ,Reference Values ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Triglycerides ,Apolipoproteins B ,Intermediate-density lipoprotein ,biology ,business.industry ,Cholesterol ,Middle Aged ,medicine.disease ,Lipoproteins, LDL ,Lipoproteins, IDL ,chemistry ,Low-density lipoprotein ,Hypertension ,biology.protein ,Female ,lipids (amino acids, peptides, and proteins) ,Lipoprotein disorder ,Lipoproteins, HDL ,business ,Lipoprotein - Abstract
The purpose of the present study was to elucidate the characteristic lipoprotein disorder in essential hypertension. Twenty-six patients with essential hypertension (HT) but without diabetes mellitus or obesity and 24 healthy subjects (control) were recruited into this study. Lipoproteins of HT and controls were separated by ultracentrifugation to very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low-density liproprotein (LDL), and (HDL) fractions. Cholesterol and triglycerides were determined with enzyme assay, and apoB were determined by highly sensitive latex agglutination (Kyowa-hakko Co. LD). There was no difference in age (mean +/- SE; HT, 63 +/- 2 versus control, 60 +/- 2 years) or body-mass index (22.7 +/- 0.4 versus 21.7 +/- 0.5 kg/m2) between HT and controls. Blood pressure in HT and controls was 158 +/- 2/87 +/- 12 mm Hg and 123 +/- 3/72 +/- 2 mm Hg, respectively. Cholesterol did not change significantly in plasma (192.1 +/- 7.0 versus 176.4 +/- 4.2 mg/dL), VLDL (15.2 +/- 2.4 versus 11.8 +/- 1.7 mg/dL), IDL (14.8 +/- 2.4 versus 10.7 +/- 1.6 mg/dL), LDL (93.7 +/- 4.6 versus 83.1 +/- 3.9 mg/dL), nor in HDL (51.9 +/- 2.7 versus 58.1 +/- 3.2 mg/dL). Triglycerides (TG) increased in plasma (120.0 +/- 10.0 versus 87.5 +/- 9.3 mg/dL, p < 0.05), although TG did not change in all subfractions. ApoB increased in plasma (105.5 +/- 5.1 versus 85.6 +/- 3.6 mg/dL, p < 0.01), IDL (9.0 +/- 1.3 versus 5.4 +/- 0.6 mg/dL, p < 0.05), and LDL (76.3 +/- 4.3 versus 59.4 +/- 3.7 mg/dL, p < 0.01) in HT compared with controls. The ratio of cholesterol to apoB in LDL decreased (1.27 +/- 0.06 versus 1.48 +/- 0.08, p < 0.05). In essential HT, number of apoB containing lipoproteins (IDL, LDL) increased. Low ratio of cholesterol to apoB was noted in LDL, indicating the presence of small, dense LDL. As cholesterol in LDL was normal, hyperbetalipoproteinemia is also a characteristic disorder of essential HT.
- Published
- 1995
15. Development of approximate formula for LDL-chol, LDL-apo B and LDL-chol/LDL-apo B as indices of hyperapobetalipoproteinemia and small dense LDL
- Author
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Yutaka Harano, Toshifumi Mannami, Motoyoshi Ikebuchi, Motoo Tsushima, Masami Yoshida, Yoko Tokunaga, Yasushi Hara, Masaaki Suzuki, Makoto Takeuchi, Yuichi Hattori, Ying Wang, Di Zhao, Syunnroku Baba, Hiroshi Kishioka, and Kayoko Ryomoto
- Subjects
medicine.medical_specialty ,Very low-density lipoprotein ,Small dense ldl ,Hyperlipoproteinemias ,Apolipoprotein B ,Arteriosclerosis ,Population ,Models, Biological ,Internal medicine ,polycyclic compounds ,medicine ,Humans ,education ,Apolipoproteins B ,Ldl cholesterol ,education.field_of_study ,biology ,Chemistry ,technology, industry, and agriculture ,Cholesterol, LDL ,Ldl chol ,Lipoproteins, LDL ,Endocrinology ,Type iib ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine ,Lipoprotein - Abstract
Estimation of LDL-chol and LDL-apo B is useful for the diagnosis of hyperapobetalipoproteinemia (normal LDL-chol with increased LDL-apo B), which is one of the most commonly occurring lipoprotein disorders associated with atherosclerotic cardiovascular diseases. The LDL-chol/LDL-apo B ratio reflects the level of small dense LDL, which is an important risk factor for IHD, CVD and ASO. In order to estimate LDL-apo B and LDL-chol/LDL-apo B ratio from blood chol, TG, HDL-chol and apo B values, we developed a formula for LDL-chol ¿0.94Chol- 0.94HDL-chol - 0.19TG¿, LDL-apo B ¿apo B - 0.09Chol + 0.09HDL-chol-0.08TG¿, and LDL-chol/LDL-apo B [¿0.94Chol-0.94HDL-chol - 0.19TG¿/¿apo B - 0.09Chol + 0.09HDL-chol-0.08TG¿] using ultracentrifugal data from 2179 subjects. These were calculated by the least squares method on the assumption that a certain compositional relationship exists between Chol, TG and apo B in VLDL, IDL and LDL. Friedewald's formula for LDL-chol (Chol - HDL-chol - 0.2TG) includes IDL-chol, but the present new formula theoretically excludes IDL-chol. It suggests a better estimation for the correct LDL-chol. Estimated LDL-apo B is useful for the diagnosis of hyperapobetalipoproteinemia and detection of small dense LDL. Without performing ultracentrifuge, additional information is obtained for the quantitative and qualitative alteration of LDL, such as small dense LDL. The above formulae and a new classification of lipoproteinemia including apo B were applied to the analyses of lipoprotein profiles of subjects with cardiovascular diseases, which were compared with those in the general population. Hyperapobetalipoproteinemia with high TG was observed 2-3 times more frequently in subjects with CAD, MI and ASO than in the Suita population. Lower ratios of LDL-chol/LDL-apo B, reflecting preponderance of small dense LDL, were observed in the above three groups. Type IIb and combined low HDL-chol were also frequent phenotypes in CAD, A-Th and ASO. The present formulae are useful for the detailed analyses of lipoprotein disorders in both qualitative as well as quantitative aspects.
- Published
- 1998
16. Mechanism and clinical implication of insulin resistance syndrome
- Author
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Masaaki Suzuki, Motoo Tsushima, Yutaka Harano, Kazuya Shinozaki, Motoyoshi Ikebuchi, Yasushi Hara, and Tatsuo Matsuyama
- Subjects
Blood Platelets ,medicine.medical_specialty ,Arteriosclerosis ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Coronary Disease ,Cilazapril ,Essential hypertension ,Angina Pectoris ,Impaired glucose tolerance ,Insulin resistance ,Catecholamines ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Internal Medicine ,medicine ,Hyperinsulinemia ,Humans ,Insulin ,Pancreatic hormone ,Antihypertensive Agents ,business.industry ,Body Weight ,Syndrome ,medicine.disease ,Endocrinology ,Tissue Plasminogen Activator ,Hypertension ,Prostaglandins ,Calcium ,Insulin Resistance ,business ,Dyslipidemia ,medicine.drug - Abstract
The insulin resistance syndrome has been noted as an interesting and important new risk factor for coronary artery disease. The syndrome consists of hypertension, glucose intolerance, and dyslipidemia, all of which are likely to be derived from insulin insensitivity. In subjects with nonobese and nondiabetic essential hypertension, steady-state plasma glucose (SSPG) was higher than in normotensive subjects during an insulin sensitivity test, indicating reduced insulin sensitivity to glucose metabolism in the hypertensive group. SSPG correlated with the percentage decrease of branched chain amino acids, free fatty acids, and serum potassium during the insulin sensitivity test. With a 2-h insulin infusion, serum norepinephrine, epinephrine, plasminogen activator inhibitor 1, and intraplatelet Ca2+ decreased significantly, but 6-ke-to-prostaglandin (PG) F1α and PGE2 did not change. Insulin resistance decreased by using antihypertensive treatments with bunazosin, cilazapril, amlodipine, and benidipine in hypertensive subjects. Diagnostic criteria for the insulin resistance syndrome, including clinical values for each risk factor, were developed. Lowered insulin sensitivity and hyperinsulinemia were demonstrated in subjects with both vasospastic and coronary artery stenotic angina. The insulin resistance syndrome together with hyperinsulinemia is likely to induce atherosclerotic changes, possibly through reduced rather than excessive action of insulin.
- Published
- 1996
17. Glycation, oxidative stress, and scavenger activity: glucose metabolism and radical scavenger dysfunction in endothelial cells
- Author
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Atunori Kashiwagi, Yoshihiko Nishio, Yasushi Tanaka, Motoyoshi Ikebuchi, Takayuki Asahina, Ryuichi Kikkawa, and Yukio Shigeta
- Subjects
medicine.medical_specialty ,Umbilical Veins ,Endocrinology, Diabetes and Metabolism ,Pentose phosphate pathway ,medicine.disease_cause ,Pentose Phosphate Pathway ,chemistry.chemical_compound ,Polyol pathway ,Glycation ,Internal medicine ,Internal Medicine ,medicine ,Diabetes Mellitus ,Humans ,Glycolysis ,Cells, Cultured ,Chemistry ,Superoxide Dismutase ,Glutathione ,Hydrogen Peroxide ,Endothelial stem cell ,Oxidative Stress ,Endocrinology ,Glucose ,Endothelium, Vascular ,Reactive Oxygen Species ,Oxidation-Reduction ,Intracellular ,Oxidative stress ,NADP - Abstract
It has been reported that oxidative stress is increased in vivo in the diabetic state. Increased oxidative stress is caused not only by accelerated production of oxygen-free radicals but also by decreased scavenging of those molecules. Endothelial cells are extremely sensitive to oxidative stress, resulting in impairments of various endothelial cell function. In this report, we studied the association of intracellular glucose metabolism and oxygen radical scavenging function via the glutathione redox (GR) cycle in cells exposed to high-glucose conditions using cultured human umbilical vein endothelial cells. Glutathione-dependent H2O2 degradation in cells exposed to 33 mmol/1 glucose (HG) for 5–7 days was reduced by 48% vs. 5.5 mmol/1 glucose (NG). This impairment under the oxidative stress was D-glucose-specific and concentration-dependent and was also associated with a 42% decrease in intracellular NADPH content. Exposure of cells to 200 μmol/1 H2O2 stimulated the GR cycle and the pentose phosphate pathway (PPP) at the same time. In the HG condition, activation of PPP was reduced by 50%, which was consistent with a decrease in NADPH content. Inhibition of glycolysis by H2O2 was less marked in HG cells versus NG cells. Activation of polyol pathway in HG cells is not responsible for the decrease in intracellular NADPH content. These results indicate that activation of the PPP and NADPH supply to the GR cycle is impaired in HG cells exposed to H2O2, which may result in increased oxidative stress to endothelial cells.
- Published
- 1996
18. Improvement of insulin sensitivity and dyslipidemia with a new alpha-glucosidase inhibitor, voglibose, in nondiabetic hyperinsulinemic subjects
- Author
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J. Hirose, Motoyoshi Ikebuchi, Yutaka Harano, M. Suzuki, K Shinozaki, and Y Hara
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Hyperlipidemias ,Carbohydrate metabolism ,Endocrinology ,Internal medicine ,Hyperinsulinism ,Voglibose ,Blood plasma ,Hyperinsulinemia ,medicine ,Humans ,Insulin ,Glycoside Hydrolase Inhibitors ,Enzyme Inhibitors ,Pancreatic hormone ,Chemistry ,Area under the curve ,Middle Aged ,medicine.disease ,Cyclohexanols ,Female ,Dyslipidemia ,medicine.drug - Abstract
This study was undertaken to investigate the effect of voglibose, a new alpha-glucosidase inhibitor, on glucose and lipid metabolism in nondiabetic hyperinsulinemic subjects. Sixteen nondiabetic subjects with hyperinsulinemia participated in the study. They were divided into two groups of eight subjects with normal (NGT) and impaired (IGT) glucose tolerance. A meal tolerance test and a 75-g oral glucose tolerance test (OGTT) were performed at the beginning (baseline phase) and end (treatment phase) of the 12-week treatment. Serum lipid levels were measured every 4 weeks throughout the treatment phase and follow-up phase (8 weeks). All patients received 1 0.2-mg tablet of voglibose before each test meal (3 tablets per day). We also measured insulin sensitivity using a steady-state plasma glucose (SSPG) method in eight normotensive hyperinsulinemic subjects and in eight age- and body mass index (BMI)-matched control subjects before and after the drug treatment. Voglibose significantly decreased the responses of plasma glucose and insulin on the meal tolerance test. The area under the curve for 2-hour insulin during the 75-g OGTT decreased after treatment, whereas that for 2-hour glucose did not change before and after treatment. SSPG was reduced after treatment, indicating improvement of insulin sensitivity. Moreover, treatment with voglibose resulted in a significant decline of triglyceride level and an elevation of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1. These values returned to near-baseline levels after the drug was discontinued. Consequently, we conclude that this agent not only has a direct hypoglycemic effect through decreased absorption of carbohydrate, but also a hypoinsulinemic and hypolipidemic effect via improved insulin sensitivity.
- Published
- 1996
19. Modified method using a somatostatin analogue, octreotide acetate (Sandostatin) to assess in vivo insulin sensitivity
- Author
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Ryohei Todo, Junya Hirose, Yutaka Harano, Kazuya Shinozaki, Motoyoshi Ikebuchi, Chiaki Yokota, Kayoko Ikeda, Masaaki Suzuki, and Aristune Kageyama
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Octreotide acetate ,Octreotide ,Modified method ,Glucagon ,Endocrinology ,Bolus (medicine) ,In vivo ,Internal medicine ,medicine ,Humans ,Insulin ,C-Peptide ,Chemistry ,Insulin sensitivity ,Middle Aged ,Hormones ,Kinetics ,Somatostatin ,Hypertension ,Female ,Insulin Resistance ,medicine.drug - Abstract
In order to evaluate the steady state plasma glucose (SSPG) method by using a new somatostatin derivative, octreotide acetate (Sandostatin) instead of somatostatin that we had used for the insulin sensitivity test, we examined whether octreotide was able to suppress C-peptide (CPR), glucagon (IRG), and GH to a similar degree to that achieved with somatostatin. A total of 52 studies were performed in 45 essential hypertensive subjects and 7 healthy subjects. Octreotide was given subcutaneously in a does of 50 micrograms or 100 micrograms 10 min before the test (sc 50, sc 100 groups) or intravenously infused over 2 h (10 micrograms in bolus followed by a constant infusion, 50, 100, or 150 micrograms/2 h: i.v. 50, i.v. 100, i.v. 150 groups). In all of the groups the plasma immunoreactive insulin (IRI) concentration increased gradually after insulin injection and reached the steady state plasma insulin (SSPI) level between 40 and 60 microU/ml at 60 min through 120 min. Plasma CPR at 120 min was the most suppressed (by 67% of the basal level in i.v. 150 group during the study period), but on the other hand in both the sc 100 and i.v. 100 groups the plasma CPR concentration at 120 min was suppressed by nearly 40%, but not significantly suppressed in either the sc 50 or the i.v. 50 group. Plasma IRG and GH were strongly suppressed after 60 min in all groups during the study period. Plasma glucose had increased significantly at 30 min and reached the steady state at 90 min through 120 min in hypertensive and healthy subjects. The results indicated that the modified SSPG method with continuous intravenous infusion of Octreotide at 150 micrograms/2 h was adequate for the measurement of insulin sensitivity.
- Published
- 1996
20. Demonstration of insulin resistance in coronary artery disease documented with angiography
- Author
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Yutaka Harano, Yasushi Hara, Kazuya Shinozaki, Motoyoshi Ikebuchi, and Masaaki Suzuki
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Epinephrine ,Systole ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Lipoproteins ,Coronary Disease ,Coronary Angiography ,Coronary artery disease ,Norepinephrine ,Insulin resistance ,Diastole ,Internal medicine ,Diabetes mellitus ,Glucose Intolerance ,Internal Medicine ,Hyperinsulinemia ,Medicine ,Humans ,Insulin ,Coronary atherosclerosis ,Triglycerides ,Aged ,Advanced and Specialized Nursing ,Glucose tolerance test ,medicine.diagnostic_test ,business.industry ,Smoking ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Endocrinology ,Apolipoproteins ,Cholesterol ,Cardiology ,Regression Analysis ,Female ,Insulin Resistance ,business ,Dyslipidemia - Abstract
OBJECTIVE To evaluate the relation between insulin resistance and coronary atherosclerosis, insulin sensitivity in lean nondiabetic, normotensive subjects with and without obstructive coronary artery disease (CAD). The correlation between insulin resistance and degree of coronary stenosis was also investigated. RESEARCH DESIGN AND METHODS Four groups were studied: 1) nine subjects with normal glucose tolerance(NGT) without CAD, 2) 10 subjects with NGT with CAD, 3) nine subjects withimpaired glucose tolerance (IGT) without CAD, and 4) 10 subjects with IGT with CAD. Insulin sensitivity was determined by the steady-state plasma glucose (SSPG) method using Sandostatin. Coronary angiography was performed in all study subjects, and the severity of coronary artery atherosclerosis wasquantified in a modified Gensini score. RESULTS The SSPG (millimoles per liter) levels were significantly higher in the patients with CAD compared with control subjects (control vs. patient group: 4.8 ±0.5 vs. 7.9 ± 0.9 with NGT, P < 0.05; 5.6 ± 0.5 vs. 11.1 ± 0.8 with IGT, P < 0.001), indicating the presence of insulin resistance in patients with CAD. The coronary atherosclerosis score (CAS) was significantly and positively correlated with SSPG (r = 0.74, P < 0.05) and 2-h insulin area (r = 0.78, P < 0.01) in NGT subjects with CAD. On the other hand, the percentage fall of plasma free fatty acid (0–30 min) during an insulin sensitivity test was significantly decreased in the subjects with CAD and was inversely correlated with the CAS (r = −0.43, P < 0.05), especially in NGT subjects with CAD. CONCLUSIONS These data suggest that in patients with CAD, insulin-mediated glucose metabolism is significantly impaired, and a significant correlation was noted between insulin resistance and severity of CAD. Therefore, the hyperinsulinemia often observed in patients with CAD is attributable to the compensatory mechanism of the β-cell to the inadequate action of insulin for glucose metabolism. Hyperinsulinemia in the presence of insulin resistance aggravates dyslipidemia and may stimulate the atheromatous process by an as-yet-unknown mechanism.
- Published
- 1996
21. Role of insulin resistance associated with compensatory hyperinsulinemia in ischemic stroke
- Author
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Motoyoshi Ikebuchi, Tohru Sawada, Masaaki Suzuki, Kazuya Shinozaki, Yutaka Harano, Hiroaki Naritomi, and Takao Shimizu
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Heart Diseases ,medicine.medical_treatment ,Infarction ,Octreotide ,Brain Ischemia ,Insulin resistance ,Gastrointestinal Agents ,Internal medicine ,Hyperinsulinism ,medicine ,Hyperinsulinemia ,Humans ,Insulin ,cardiovascular diseases ,Stroke ,Triglycerides ,Aged ,Apolipoproteins B ,Embolism, Cholesterol ,Advanced and Specialized Nursing ,business.industry ,Cerebral infarction ,Cerebral Infarction ,Glucose Tolerance Test ,Intracranial Embolism and Thrombosis ,Middle Aged ,medicine.disease ,Lipids ,Cerebral Angiography ,Cerebrovascular Disorders ,Endocrinology ,Female ,Neurology (clinical) ,Insulin Resistance ,Cardiology and Cardiovascular Medicine ,business ,Lipoproteins, HDL ,Compensatory Hyperinsulinemia - Abstract
Background and Purpose Although insulin resistance and hyperinsulinemia play a crucial role in the pathogenesis of atherosclerosis, little is known about their roles in ischemic stroke. The purpose of this study was to clarify whether insulin resistance and hyperinsulinemia are causative factors in the pathogenesis of ischemic stroke. Methods Thirty-four consecutive patients with ischemic stroke, who were normotensive, nondiabetic, and not obese, were classified into three groups—atherothrombotic infarction (n=16), lacunar infarction (n=10), and cardioembolic infarction (n=8)—based on clinical findings, brain imaging, and cerebral angiography. Both oral glucose tolerance tests and lipid analyses were performed. Insulin sensitivity was determined by the steady state plasma glucose method with the use of octreotide acetate. Data were compared with those of healthy control subjects (n=15). Results Steady state plasma glucose levels were significantly higher in the atherothrombotic infarction group compared with control subjects and the other two stroke groups, indicating the presence of insulin resistance in patients with atherothrombotic infarction. In the atherothrombotic infarction group, the 2-hour insulin area (area under the plasma insulin concentration curve) during a 75-g oral glucose tolerance test was significantly increased and dyslipidemic changes (increased triglyceride and apolipoprotein B, decreased high-density lipoprotein) were observed, whereas these changes were not found in the lacunar infarction and cardioembolic stroke groups. Conclusions Insulin resistance in association with compensatory hyperinsulinemia and dyslipidemia may be an important pathogenetic factor underlying the development of atherothrombotic infarction.
- Published
- 1996
22. Normalization of insulin resistance in non-obese essential hypertension by cilazapril treatment
- Author
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Masaaki Suzuki, Yutaka Harano, Kazuya Shinozaki, Motoyoshi Ikebuchi, and Chiaki Yokota
- Subjects
Male ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Cilazapril ,Essential hypertension ,Insulin resistance ,Catecholamines ,Internal medicine ,Internal Medicine ,medicine ,Hyperinsulinemia ,Humans ,Obesity ,Pancreatic hormone ,Antihypertensive Agents ,business.industry ,Insulin ,Captopril ,General Medicine ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Lipids ,Endocrinology ,ACE inhibitor ,Hypertension ,Female ,Insulin Resistance ,business ,medicine.drug - Abstract
To determine whether ACE inhibitor other than captopril improves insulin sensitivity in patients with essential hypertension, we measured insulin sensitivity to glucose utilization using SSPG method in 10 lean hypertensive subjects before and after chronic cilazapril treatment (1.5 +/- 0.2 mg/day, 15.6 +/- 2.1 weeks). The results were compared with those obtained in 10 healthy control subjects. SSPG obtained by insulin sensitivity test was significantly higher in hypertensive subjects, indicating a lower insulin sensitivity than in controls. After cilazapril treatment, SSPG reduced significantly to the level which was statistically not different from control subjects. Hyperinsulinemia diminished after treatment, while no significant change of blood glucose was observed during oral glucose tolerance test in hypertensive subjects. Plasma HDL cholesterol increased by cilazapril treatment. Cilazapril treatment has beneficial effect in the reversal of insulin resistance in patients with essential hypertension.
- Published
- 1995
23. Insulin resistance rather than hyperinsulinemia more closely associated with essential hypertension
- Author
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Masaaki Suzuki, Mihoko Norioka, Motoyoshi Ikebuchi, Kazuya Shinozaki, Yutaka Harano, Kayoko Ikeda, and Chiaki Yokota
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Glucose Clearance ,Physiology ,medicine.medical_treatment ,Radioimmunoassay ,Blood Pressure ,Essential hypertension ,Insulin resistance ,Catecholamines ,Internal medicine ,Hyperinsulinism ,Internal Medicine ,medicine ,Hyperinsulinemia ,Humans ,Pancreatic hormone ,Chromatography, High Pressure Liquid ,Analysis of Variance ,business.industry ,Insulin ,Sodium ,General Medicine ,Middle Aged ,medicine.disease ,Pathophysiology ,Endocrinology ,Blood pressure ,Spectrometry, Fluorescence ,Hypertension ,Regression Analysis ,Female ,Insulin Resistance ,business - Abstract
In order to clarify which of the two, insulin resistance or hyperinsulinemia, are more contributable to non obese and non diabetic hypertension, insulin sensitivity test was performed. By multiple regression analysis, mean, systolic, and diastolic blood pressure were inversely correlated with glucose clearance. During insulin sensitivity test, plasma catecholamines levels and FENa were not changed by insulin infusion. In the present study, it is demonstrated that insulin has no hypertensive effect under the mild hyperinsulinemia (45-55 microU/ml). We conclude that insulin resistance rather than hyperinsulinemia may be more closely associated with non obese and non diabetic hypertension.
- Published
- 1995
24. Increase in cardiac muscle fructose content in streptozotocin-induced diabetic rats
- Author
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Motoyoshi Ikebuchi, Tsutomu Ogawa, Masashi Suzaki, Yoshikazu Saeki, Yukio Shigeta, Toshiyuki Obata, Yoshifumi Takagi, Yasuo Kida, Atsunori Kashiwagi, Takayuki Asahina, Yasushi Tanaka, and Ryuichi Kikkawa
- Subjects
Male ,medicine.medical_specialty ,L-Iditol 2-Dehydrogenase ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Fructose ,Gas Chromatography-Mass Spectrometry ,Streptozocin ,Diabetes Mellitus, Experimental ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Endocrinology ,Polyol pathway ,Aldehyde Reductase ,Diabetes mellitus ,Internal medicine ,Medicine ,Animals ,Sorbitol ,business.industry ,Insulin ,Cardiac muscle ,Carbohydrate ,Papillary Muscles ,Streptozotocin ,medicine.disease ,Rats ,carbohydrates (lipids) ,medicine.anatomical_structure ,chemistry ,business ,Inositol ,medicine.drug - Abstract
To evaluate the activation of the sorbitol pathway in cardiac muscle in diabetic rats, we measured sorbitol, fructose, and myo-inositol content in cardiac tissue obtained from control and streptozotocin-diabetic rats, with or without an 8-week insulin treatment, using gas chromatography-mass spectrometry (GC-MS). Cardiac fructose and sorbitol content in 10-week diabetic rats increased by 60-fold and 3.9-fold of those of control rats, respectively (P less than .001). In contrast, cardiac myo-inositol content in 10-week diabetic rats decreased to 56% (P less than .025) of the control value. The abnormalities in cardiac fructose, sorbitol, and myo-inositol content were completely normalized by the 8-week insulin treatment, which was initiated 2 weeks after the induction of diabetes. There was no difference in cardiac aldose reductase activity between control and diabetic rats. However, cardiac sorbitol dehydrogenase activity in diabetic rats was 151% (P less than .005) higher than that of control rats, although hepatic sorbitol dehydrogenase activity was not different between the two groups. These results indicate that the sorbitol pathway is significantly activated in cardiac tissue obtained from streptozotocin-induced diabetic rats, which results in the marked cardiac accumulation of fructose.
- Published
- 1992
25. Increases in Voltage-Sensitive Calcium Channel of Cardiac and Skeletal Muscle in Streptozotocin-Induced Diabetic Rats
- Author
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Yoshihiko Nishio, M. Kodama, Takayuki Asahina, Motoyoshi Ikebuchi, Yukio Shigeta, Atsunori Kashiwagi, Tsutomu Ogawa, and S. Tanaka
- Subjects
medicine.medical_specialty ,Nucleotidase activity ,business.industry ,Cardiac muscle ,Dihydropyridine ,Cardiomyopathy ,Skeletal muscle ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,Diabetic cardiomyopathy ,Internal medicine ,medicine ,Verapamil ,Channel blocker ,business ,medicine.drug - Abstract
Many lines of evidence including epidemiological (1), clinical (2,3) and experimental (4,5) studies have shown the existence of specific abnormalities in cardiac muscle in diabetes. Recently, it has been suggested that Ca2+ overload into cardiac muscle may be one of the contributing factors for cardiomyopathy (6). Furthermore, an increase in tissue Ca2+ level has been reported in chronic diabetic rats (7), which may be associated with cardiomyopathy in diabetes (8). Interestingly, Afzal N. et al. (9) have shown that treatment of streptozotocin-diabetic rats with verapamil, a voltage- sensitive Ca2+ channel blocker, improves cardiac dysfunction. These reports suggest that an excess Ca2+ influx through voltage-sensitive Ca2+ channel may induce cardiomyopathy in diabetes. However, there has been no report on voltage sensitive Ca2+ channel in diabetic rat heart. Therefore, in the present study, we have examined the status of Ca2+ channels in cardiac muscle as well as skeletal muscle membrane from control and streptozotocin- induced diabetic rats using [3H]PN200-110, a dihydropyridine derivative as a ligand.
- Published
- 1992
26. Increase in [3H]PN 200-110 binding to cardiac muscle membrane in streptozocin-induced diabetic rats
- Author
-
Motoyoshi Ikebuchi, Mitsuaki Kodama, Yoshihiko Nishio, Takayuki Asahina, Atsunori Kashiwagi, Yukio Shigeta, and Tsutomu Ogawa
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Peptide hormone ,In Vitro Techniques ,Tritium ,Streptozocin ,Diabetes Mellitus, Experimental ,Internal medicine ,Internal Medicine ,medicine ,Myocyte ,Animals ,Insulin ,Oxadiazoles ,Binding Sites ,Membranes ,Chemistry ,Myocardium ,Cardiac muscle ,Dihydropyridine ,Rats, Inbred Strains ,Streptozotocin ,Rats ,Endocrinology ,medicine.anatomical_structure ,Verapamil ,Cardiovascular agent ,Calcium ,Isradipine ,medicine.drug - Abstract
Voltage-sensitive Ca2+ channels in cardiac left ventricular muscle membranes isolated from nondiabetic control and diabetic rats were measured with (3H)PN 200-110, a dihydropyridine derivative, as a ligand. The binding site (Bmax) of (3H)PN 200-110 in cardiac membranes isolated from streptozocin-induced diabetic (STZ-D) rats (128 +/- 10 fmol/mg protein) significantly (P less than 0.01) increased by 64% compared with that of control rats (78 +/- 4 fmol/mg protein) 10 wk after STZ administration without a significant change in Kd. However, the significant increase in Bmax of (3H)PN 200-110 binding in diabetic rats depended on the duration of diabetes such that the increase was not found until 6 wk after STZ injection. An 8-wk intensive insulin treatment, which was initiated 2 wk after STZ injection, normalized the increase in (3H)PN 200-110 binding in STZ-D rats to control levels (85 +/- 4 fmol/mg protein). Furthermore, (3H)PN 200-110 binding to control cardiac membranes was dose-dependently inhibited in the presence of verapamil, a phenylalkylamine Ca2+ antagonist, but that was not the case in cardiac membranes isolated from STZ-D rats. These results indicate that voltage-sensitive Ca2+ channels in cardiac muscle isolated from STZ-D rats are quantitatively and qualitatively altered, because the course of diabetes and themore » increase in the channels can be prevented by treatment with insulin.« less
- Published
- 1990
27. Effect of verapamil on cardiac protein kinase C activity in diabetic rats
- Author
-
Yasushi, Tanaka, primary, Atsunori, Kashiwagi, additional, Tsutomu, Ogawa, additional, Nanami, Abe, additional, Takayuki, Asahina, additional, Motoyoshi, Ikebuchi, additional, Yoshihumi, Takagi, additional, and Yukio, Shigeta, additional
- Published
- 1991
- Full Text
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