138,334 results on '"Glucose metabolism"'
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2. Impact of Passive Heat on Metabolic, Inflammatory and Vascular Health in Persons With Spinal Cord Injury (SCIPHS)
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- 2024
3. Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy
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Joslin Diabetes Center, University of Siena, University of Copenhagen, Istituto di Neuroscienze Consiglio Nazionale delle Ricerche, University of Pisa, and Giaccari Andrea, associate professor
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- 2024
4. GENESIS: Genotype Guided - Natriuretic Peptides - Cardiometabolic Health Study
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National Heart, Lung, and Blood Institute (NHLBI) and Pankaj Arora, MD, Assistant Professor, Division of Cardiovascular Disease, Department of Medicine
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- 2024
5. The Impact of Glycemic Index on Sleep and Memory Consolidation
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Dr Hayley Young, Associate Professor
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- 2024
6. Diurnal Variation of Exercise on Metabolic Health (DIVA)
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Jonatan Ruiz Ruiz, Director
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- 2024
7. Mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.
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Fu, Liwan, Cheng, Hong, Xiong, Jingfan, Xiao, Pei, Shan, Xinying, Li, Yanyan, Li, Yan, Zhao, Xiaoyuan, and Mi, Jie
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Objective Methods Results Conclusions The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6–18 years who underwent dual‐energy X‐ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta‐Analysis of Glucose and Insulin‐Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH).In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA‐IR) and homeostasis model assessment of pancreatic beta cell function (HOMA‐β) through FGF23, whereas fat‐free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat‐free mass with fasting glucose, fasting insulin and HOMA‐IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat‐free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01–1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77–0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: −0.05 [95% CI: −0.07, −0.02]) and fat‐free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose.Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Baseline SUVmax is correlated with tumor hypoxia and patient outcomes in nasopharyngeal carcinoma.
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Ding, Jianming, Liqian, Lin, Yuhao, Zheng, Xiaobing, Huang, Chaoxiong, Hong, Jiabiao, Chen, Chuanben, and Fei, Zhaodong
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NASOPHARYNX cancer , *HYPOXEMIA , *GLUCOSE metabolism , *SURVIVAL rate , *TREATMENT effectiveness , *PROGRESSION-free survival , *SURVIVAL analysis (Biometry) - Abstract
To evaluate the prognostic significance of the maximum standardized uptake value (SUVmax) in nasopharyngeal carcinoma (NPC), establish a gene signature that correlates with SUVmax, and explore the underlying biological behaviors associated with these correlations for the prediction of clinical outcomes. A cohort of 726 patients with NPC was examined to identify correlations between SUVmax and various clinical variables. RNA sequencing was performed to identify genes related to SUVmax, and these genes were used to develop an SUV signature. Additionally, transcriptome enrichment analysis was conducted to investigate the potential biological behaviors underlying the observed correlations. Higher SUVmax was associated with an increased tumor burden and worse prognosis. The SUV signature, which consisted of 10 genes, was positively correlated with SUVmax, and it predicted worse survival outcomes. This signature was highly expressed in malignant epithelial cells and associated with hypoxia and resistance to radiotherapy. Additionally, the signature was negatively correlated with immune function. SUVmax is a valuable prognostic indicator in NPC, with higher values predicting worse outcomes. The SUV signature offers further prognostic insights, linking glucose metabolism to tumor aggressiveness, treatment resistance, and immune function, and it could represent a potential biomarker for NPC. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Hypoxia-inducible factor-driven glycolytic adaptations in host-microbe interactions.
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DeMichele, Emily, Buret, Andre G., and Taylor, Cormac T.
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HYPOXIA-inducible factors , *CELL physiology , *BACTERIAL diseases , *GLUCOSE metabolism , *BIOCHEMICAL substrates - Abstract
Mammalian cells utilize glucose as a primary carbon source to produce energy for most cellular functions. However, the bioenergetic homeostasis of cells can be perturbed by environmental alterations, such as changes in oxygen levels which can be associated with bacterial infection. Reduction in oxygen availability leads to a state of hypoxia, inducing numerous cellular responses that aim to combat this stress. Importantly, hypoxia strongly augments cellular glycolysis in most cell types to compensate for the loss of aerobic respiration. Understanding how this host cell metabolic adaptation to hypoxia impacts the course of bacterial infection will identify new anti-microbial targets. This review will highlight developments in our understanding of glycolytic substrate channeling and spatiotemporal enzymatic organization in response to hypoxia, shedding light on the integral role of the hypoxia-inducible factor (HIF) during host–pathogen interactions. Furthermore, the ability of intracellular and extracellular bacteria (pathogens and commensals alike) to modulate host cellular glucose metabolism will be discussed. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Metabolic characteristics of transmembrane prolyl 4-hydroxylase (P4H-TM) deficient mice.
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Ala-Nisula, Tuulia, Halmetoja, Riikka, Leinonen, Henri, Kurkela, Margareta, Lipponen, Henna-Riikka, Sakko, Samuli, Karpale, Mikko, Salo, Antti M., Sissala, Niina, Röning, Tapio, Raza, Ghulam S., Mäkelä, Kari A., Thevenot, Jérôme, Herzig, Karl-Heinz, Serpi, Raisa, Myllyharju, Johanna, Tanila, Heikki, Koivunen, Peppi, and Dimova, Elitsa Y.
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BLOOD lactate , *FREE fatty acids , *CENTRAL nervous system , *GLUCOSE metabolism , *ENERGY metabolism , *HOMEOSTASIS - Abstract
Transmembrane prolyl 4-hydroxylase (P4H-TM) is an enigmatic enzyme whose cellular function and primary substrate remain to be identified. Its loss-of-function mutations cause a severe neurological HIDEA syndrome with hypotonia, intellectual disability, dysautonomia and hypoventilation. Previously, P4H-TM deficiency in mice was associated with reduced atherogenesis and lower serum triglyceride levels. Here, we characterized the glucose and lipid metabolism of P4h-tm−/− mice in physiological and tissue analyses. P4h-tm−/− mice showed variations in 24-h oscillations of energy expenditure, VO2 and VCO2 and locomotor activity compared to wild-type (WT) mice. Their rearing activity was reduced, and they showed significant muscle weakness and compromised coordination. Sedated P4h-tm−/− mice had better glucose tolerance, lower fasting insulin levels, higher fasting lactate levels and lower fasting free fatty acid levels compared to WT. These alterations were not present in conscious P4h-tm−/− mice. Fasted P4h-tm−/− mice presented with faster hepatic glycogenolysis. The respiratory rate of conscious P4h-tm−/− mice was significantly lower compared to the WT, the decrease being further exacerbated by sedation and associated with acidosis and a reduced ventilatory response to both hypoxia and hypercapnia. P4H-TM deficiency in mice is associated with alterations in whole-body energy metabolism, day-night rhythm of activity, glucose homeostasis and neuromuscular and respiratory functions. Although the underlying mechanism(s) are not yet fully understood, the phenotype appears to have neurological origins, controlled by brain and central nervous system circuits. The phenotype of P4h-tm−/− mice recapitulates some of the symptoms of HIDEA patients, making this mouse model a valuable tool to study and develop tailored therapies. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Point‐of‐care β‐hydroxybutyrate measurement predicts adequate glucose metabolism suppression in cardiac FDG‐PET/CT.
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Hartikainen, Suvi, Tompuri, Tuomo, Laitinen, Tiina, and Laitinen, Tomi
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HEART metabolism , *LEAN body mass , *GLUCOSE metabolism , *COMPUTED tomography , *RECEIVER operating characteristic curves - Abstract
Aims: The aims of our study were to evaluate whether point‐of‐care β‐hydroxybutyrate (BHB) measurement can be used to identify patients with adequate cardiac glucose metabolism suppression for cardiac [18F]‐fluoro‐2‐deoxy‐d‐glucose‐positron emission tomography with computerized tomography (FDG‐PET/CT) and to develop a pretest probability calculator of myocardial suppression using other metabolic factors attainable before imaging. Methods and Results: We recruited 193 patients with any clinical indication for whole body [18F]‐FDG‐PET/CT. BHB level was measured with a point‐of‐care device. Maximal myocardial standardized uptake value using lean body mass (SULmax) was measured from eight circular regions of interest with 1 cm circumference and background from left ventricular blood pool. Correlations SULmax and point‐of‐care measured BHB were analysed. The ability of BHB test to predict adequate suppression was evaluated with receiver operating characteristic analysis. Liver and spleen attenuation in computed tomography were measured to assess the presence of fatty liver. BHB level correlated with myocardial uptake and, using a cut‐off value of 0.35 mmol/L to predict adequate myocardial suppression, we reached specificity of 90% and sensitivity of 56%. Other variables to predict adequate suppression were diabetes, obesity, ketogenic diet and fatty liver. Using information attainable before imaging, we created a pretest probability calculator of inadequate myocardial glucose metabolism suppression. The area under the curve for BHB test alone was 0.802 and was 0.857 for the pretest calculator (p = 0.319). Conclusions: BHB level measured with a point‐of‐care device is useful in predicting adequate myocardial glucose metabolism suppression. More detailed assessment of other factors potentially contributing to cardiac metabolism is needed. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Frontal-striatal glucose metabolism and fatigue in patients with multiple sclerosis, long COVID, and COVID-19 recovered controls.
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Rudroff, Thorsten
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POST-acute COVID-19 syndrome , *FATIGUE (Physiology) , *GLOBUS pallidus , *CAUDATE nucleus ,BRAIN metabolism - Abstract
This study compared brain glucose metabolism using FDG-PET in the caudate nucleus, putamen, globus pallidus, thalamus, and dorsolateral prefrontal cortex (DLPFC) among patients with Long COVID, patients with fatigue, people with multiple sclerosis (PwMS) patients with fatigue, and COVID recovered controls. PwMS exhibited greater hypometabolism compared to long COVID patients with fatigue and the COVID recovered control group in all studied brain areas except the globus pallidus (effect size range 0.7–1.5). The results showed no significant differences in glucose metabolism between patients with Long COVID and the COVID recovered control group in these regions. These findings suggest that long COVID fatigue may involve non-CNS systems, neurotransmitter imbalances, or psychological factors not captured by FDG-PET, while MS-related fatigue is associated with more severe frontal-striatal circuit dysfunction due to demyelination and neurodegeneration. Symmetrical standardized uptake values (SUVs) between hemispheres in all groups imply that fatigue in these conditions may be related to global or network-level alterations rather than hemisphere-specific changes. Future studies should employ fine-grained analysis methods, explore other brain regions, and control for confounding factors to better understand the pathophysiology of fatigue in MS and long COVID. Longitudinal studies tracking brain glucose metabolism in patients with Long COVID could provide insights into the evolution of metabolic patterns as the condition progresses. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Effects of light‐intensity physical activity on cardiometabolic parameters in young adults with overweight and obesity: The SED‐ACT randomized controlled crossover trial.
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Hoffmann, Sascha W., Schierbauer, Janis, Zimmermann, Paul, Voit, Thomas, Grothoff, Auguste, Wachsmuth, Nadine, Rössler, Andreas, Lackner, Helmut K., and Moser, Othmar
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HEART beat , *YOUNG adults , *SEDENTARY behavior , *HEART metabolism , *POSTURE , *SITTING position , *STANDING position - Abstract
Aims: To investigate how a change in body position with light‐intensity physical activity (PA) 'snacks' (LIPAS, alternate sitting and standing, walking or standing continuously) compared with uninterrupted prolonged sitting affects glucose metabolism and heart rate variability (HRV) parameters in young adults with overweight and obesity. Materials and Methods: We conducted a four‐arm randomized controlled crossover trial. The following conditions were tested during an 8‐h simulated workday: uninterrupted prolonged sitting (SIT), alternate sitting and standing (SIT‐STAND; 2.5 h total), continuous standing (STAND), and continuous walking (1.0 mph; WALK). The primary outcome was to investigate how a change in body position (alternate sitting and standing, walking or standing continuously) compared with uninterrupted sitting affects mean 8‐h glucose metabolism. Secondary outcomes included the effects on 2‐h postprandial glucose concentrations, as well as on 8‐h/24‐h heart rate and HRV parameters, in the respective study arms. Capillary blood samples were drawn from an hyperemised earlobe in the fasted state and once every hour during each trial intervention by puncturing the earlobe with a lancet and collecting 20 μL of blood (Biosen S‐Line Lab+; EKF diagnostics, Barleben, Germany). HRV was assessed for 24 h including the 8‐h intervention phase, and a home phase by means of a Holter electrocardiogram. All participants received the same standardized non‐relativised breakfast and lunch during the four trial visits. Results: Seventeen individuals (eight women, mean age 23.4 ± 3.3 years, body mass index 29.7 ± 3.8 kg/m2, glycated haemoglobin level 34.8 ± 3.1 mmol/mol [5.4 ± 0.3%], body fat 31.8 ± 8.2%) completed all four trial arms. Compared with SIT (89.4 ± 6.8 mg/dL), 8‐h mean glucose was lower in all other conditions (p < 0.05) and this was statistically significant compared with WALK (86.3 ± 5.2 mg/dL; p = 0.034). Two‐hour postprandial glucose after breakfast was approximately 7% lower for WALK compared with SIT (p = 0.002). Furthermore, significant time × condition effects on HRV parameters favouring light‐intensity walking were observed (p < 0.001). Conclusions: Replacement and interruption of prolonged sitting with light‐intensity walking showed a significant blood glucose‐lowering effect and improved HRV during an 8‐h work environment in young adults with overweight and obesity. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Cerebral Glucose Metabolism Is a Valuable Predictor of Survival in Patients with Lewy Body Diseases.
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Brumberg, Joachim, Blazhenets, Ganna, Bühler, Sabrina, Fostitsch, Johannes, Rijntjes, Michel, Ma, Yilong, Eidelberg, David, Weiller, Cornelius, Jost, Wolfgang H., Frings, Lars, Schröter, Nils, and Meyer, Philipp T.
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LEWY body dementia , *DEEP brain stimulation , *PARKINSON'S disease , *POSITRON emission tomography , *GLUCOSE metabolism , *BRAIN stimulation - Abstract
Objective: Patients with Lewy body diseases have an increased risk of dementia, which is a significant predictor for survival. Posterior cortical hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (PET) precedes the development of dementia by years. We therefore examined the prognostic value of cerebral glucose metabolism for survival. Methods: We enrolled patients diagnosed with Parkinson's disease (PD), Parkinson's disease with dementia, or dementia with Lewy bodies who underwent [18F]fluorodeoxyglucose PET. Regional cerebral metabolism of each patient was analyzed by determining the expression of the PD‐related cognitive pattern (Z‐score) and by visual PET rating. We analyzed the predictive value of PET for overall survival using Cox regression analyses (age‐ and sex‐corrected) and calculated prognostic indices for the best model. Results: Glucose metabolism was a significant predictor of survival in 259 included patients (n = 118 events; hazard ratio: 1.4 [1.2–1.6] per Z‐score; hazard ratio: 1.8 [1.5–2.2] per visual PET rating score; both p < 0.0001). Risk stratification with visual PET rating scores yielded a median survival of 4.8, 6.8, and 12.9 years for patients with severe, moderate, and mild posterior cortical hypometabolism (median survival not reached for normal cortical metabolism). Stratification into 5 groups based on the prognostic index revealed 10‐year survival rates of 94.1%, 78.3%, 34.7%, 0.0%, and 0.0%. Interpretation: Regional cerebral glucose metabolism is a significant predictor of survival in Lewy body diseases and may allow an earlier survival prediction than the clinical milestone "dementia." Thus, [18F]fluorodeoxyglucose PET may improve the basis for therapy decisions, especially for invasive therapeutic procedures like deep brain stimulation in Parkinson's disease. ANN NEUROL 2024;96:539–550 [ABSTRACT FROM AUTHOR]
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- 2024
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15. The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications—2023 Diabetes , Diabetes Care , and Diabetologia Expert Forum.
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Byndloss, Mariana, Devkota, Suzanne, Duca, Frank, Hendrik Niess, Jan, Nieuwdorp, Max, Orho-Melander, Marju, Sanz, Yolanda, Tremaroli, Valentina, and Zhao, Liping
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TYPE 2 diabetes , *GUT microbiome , *GLUCOSE metabolism , *DIAGNOSIS of diabetes , *DIABETES - Abstract
This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes , Diabetes Care , and Diabetologia , which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single–time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Hyperactivity of the medial thalamus in patients with photophobia‐associated migraine.
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Suzuki, Yukihisa, Kiyosawa, Motohiro, Wakakura, Masato, and Ishii, Kenji
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GLUCOSE metabolism , *SENSES , *RISK assessment , *VISION disorders , *RADIOPHARMACEUTICALS , *DEOXY sugars , *DESCRIPTIVE statistics , *POSITRON emission tomography , *THALAMUS , *LONGITUDINAL method , *CEREBRAL cortex , *CASE-control method , *COMPARATIVE studies , *CONFIDENCE intervals , *DATA analysis software , *DISEASE risk factors ,MIGRAINE complications - Abstract
Objective: To examine cerebral functional alterations associated with sensory processing in patients with migraine and constant photophobia. Background: Migraine is a common headache disorder that presents with photophobia in many patients during attacks. Furthermore, some patients with migraine experience constant photophobia, even during headache‐free intervals, leading to a compromised quality of life. Methods: This prospective, case–control study included 40 patients with migraine (18 male and 22 female) who were recruited at an eye hospital and eye clinic. The patients were divided into two groups: migraine with photophobia group, consisting of 22 patients (10 male and 12 female) with constant photophobia, and migraine without photophobia group, consisting of 18 patients (eight male and 10 female) without constant photophobia. We used 18F‐fluorodeoxyglucose and positron emission tomography to compare cerebral glucose metabolism between the two patient groups and 42 healthy participants (16 men and 26 women). Results: Compared with the healthy group, both the migraine with photophobia and migraine without photophobia groups showed cerebral glucose hypermetabolism in the bilateral thalamus (p < 0.05, family‐wise error‐corrected). Moreover, the contrast of migraine with photophobia minus migraine without photophobia patients showed glucose hypermetabolism in the bilateral medial thalamus (p < 0.05, family‐wise error‐corrected). Conclusions: The medial thalamus may be associated with the development of continuous photophobia in patients with migraine. Plain Language Summary: Migraine attacks are often accompanied by photophobia, and some patients with migraine experience constant glare, even when they do not have a headache. We tried to understand if there are changes in the brains of patients with migraine with photophobia by comparing their brain scans to those of healthy participants. We found that the thalamus had more activity in patients with migraine who experience constant glare compared to patients with migraine who do not. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Dopamine in the regulation of glucose and lipid metabolism: a narrative review.
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Li, Zhehong, Zheng, Lifei, Wang, Jing, Wang, Liang, Qi, Yao, Amin, Buhe, Zhu, Jinxia, and Zhang, Nengwei
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LIPID metabolism ,ENERGY metabolism ,DOPAMINE receptors ,GLUCOSE metabolism ,PITUITARY gland ,DOPAMINE - Abstract
Objective: Owing to the global obesity epidemic, understanding the regulatory mechanisms of glucose and lipid metabolism has become increasingly important. The dopaminergic system, including dopamine, dopamine receptors, dopamine transporters, and other components, is involved in numerous physiological and pathological processes. However, the mechanism of action of the dopaminergic system in glucose and lipid metabolism is poorly understood. In this review, we examine the role of the dopaminergic system in glucose and lipid metabolism. Results: The dopaminergic system regulates glucose and lipid metabolism through several mechanisms. It regulates various activities at the central level, including appetite control and decision‐making, which contribute to regulating body weight and energy metabolism. In the pituitary gland, dopamine inhibits prolactin production and promotes insulin secretion through dopamine receptor 2. Furthermore, it can influence various physiological components in the peripheral system, such as pancreatic β cells, glucagon‐like peptide‐1, adipocytes, hepatocytes, and muscle, by regulating insulin and glucagon secretion, glucose uptake and use, and fatty acid metabolism. Conclusions: The role of dopamine in regulating glucose and lipid metabolism has significant implications for the physiology and pathogenesis of disease. The potential therapeutic value of dopamine lies in its effects on metabolic disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Multi-omics analysis of Au@Pt nanozyme for the modulation of glucose and lipid metabolism.
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Wang, Yanan, Zhang, Qi, Kan, Minrui, Chang, Fei, He, Xiaoyun, Cheng, Nan, and Huang, Kunlun
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LIPID metabolism , *GLUCOSE metabolism , *GOLD nanoparticles , *METABOLIC disorders , *GUT microbiome - Abstract
Au@Pt nanozyme, a bimetallic core–shell structure Au and Pt nanoparticle, has attracted significant attention due to its excellent catalytic activity and stability. Here, we propose that Au@Pt improves glucose tolerance and reduces TG after four weeks administration. The transcriptomic analysis of mouse liver tissues treated with Au@Pt nanozyme showed changes in genes related to glucose and lipid metabolism signaling pathways, including glycolysis/gluconeogenesis, pyruvate metabolism, PPAR signaling, and insulin signaling. Moreover, analysis of fecal samples from mice treated with Au@Pt nanozyme showed significant changes in the abundance of beneficial gut microbiota such as Dubosiella, Parvibacter, Enterorhabdus, Monoglobus, Lachnospiraceae_UCG-008, Lachnospiraceae_UCG-006, Lachnospiraceae_UCG-001, and Christensenellaceae_R-7_group. Combined multi-omics correlation analyses revealed that the modulation of glucose and lipid metabolism by Au@Pt was strongly correlated with changes in hepatic gene expression profiles as well as changes in gut microbial profiles. Overall, our integrated multi-omics analysis demonstrated that Au@Pt nanozyme could modulate glucose and lipid metabolism by regulating the expression of key genes in the liver and altering the composition of gut microbiota, providing new insights into the potential applications of Au@Pt nanozyme in the treatment of metabolic disorder. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Elucidating the salt-tolerant mechanism of Halomonas cupida J9 and unsterile ectoine production from lignocellulosic biomass.
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Chen, Yaping, Liu, Yujie, Meng, Yan, Jiang, Yuting, Xiong, Weini, Wang, Shufang, Yang, Chao, and Liu, Ruihua
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AMINO acid derivatives , *GLUCOSE synthesis , *CORN straw , *GLUCOSE metabolism , *BIOMASS , *LIGNOCELLULOSE - Abstract
Background: Ectoine as an amino acid derivative is widely applied in many fields, such as the food industry, cosmetic manufacturing, biologics, and therapeutic agent. Large-scale production of ectoine is mainly restricted by the cost of fermentation substrates (e.g., carbon sources) and sterilization. Results: In this study, Halomonas cupida J9 was shown to be capable of synthesizing ectoine using xylose as the sole carbon source. A pathway was proposed in H. cupida J9 that synergistically utilizes both WBG xylose metabolism and EMP glucose metabolism for the synthesis of ectoine. Transcriptome analysis indicated that expression of ectoine biosynthesis module was enhanced under salt stress. Ectoine production by H. cupida J9 was enhanced by improving the expression of ectoine biosynthesis module, increasing the intracellular supply of the precursor oxaloacetate, and utilizing urea as the nitrogen source. The constructed J9U-P8EC achieved a record ectoine production of 4.12 g/L after 60 h of xylose fermentation. Finally, unsterile production of ectoine by J9U-P8EC from either a glucose-xylose mixture or corn straw hydrolysate was demonstrated, with an output of 8.55 g/L and 1.30 g/L of ectoine, respectively. Conclusions: This study created a promising H. cupida J9-based cell factory for low-cost production of ectoine. Our results highlight the potential of J9U-P8EC to utilize lignocellulose-rich agriculture waste for open production of ectoine. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Impaired glucose metabolism and the risk of vascular events and mortality after ischemic stroke: A systematic review and meta-analysis.
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Kaynak, Nurcennet, Kennel, Valentin, Rackoll, Torsten, Schulze, Daniel, Endres, Matthias, and Nave, Alexander H.
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TRANSIENT ischemic attack , *ISCHEMIC stroke , *INSULIN resistance , *STROKE , *GLUCOSE metabolism - Abstract
Background: Diabetes mellitus (DM), prediabetes, and insulin resistance are highly prevalent in patients with ischemic stroke (IS). DM is associated with higher risk for poor outcomes after IS. Objective: Investigate the risk of recurrent vascular events and mortality associated with impaired glucose metabolism compared to normoglycemia in patients with IS and transient ischemic attack (TIA). Methods: Systematic literature search was performed in PubMed, Embase, Cochrane Library on 21st March 2024 and via citation searching. Studies that comprised IS or TIA patients and exposures of impaired glucose metabolism were eligible. Study Quality Assessment Tool was used for risk of bias assessment. Covariate adjusted outcomes were pooled using random-effects meta-analysis. Main outcomes: Recurrent stroke, cardiac events, cardiovascular and all-cause mortality and composite of vascular outcomes. Results: Of 10,974 identified studies 159 were eligible. 67% had low risk of bias. DM was associated with an increased risk for composite events (pooled HR (pHR) including 445,808 patients: 1.58, 95% CI 1.34–1.85, I2 = 88%), recurrent stroke (pHR including 1.161.527 patients: 1.42 (1.29–1.56, I2 = 92%), cardiac events (pHR including 443,863 patients: 1.55, 1.50–1.61, I2 = 0%), and all-cause mortality (pHR including 1.031.472 patients: 1.56, 1.34–1.82, I2 = 99%). Prediabetes was associated with an increased risk for composite events (pHR including 8,262 patients: 1.50, 1.15–1.96, I2 = 0%) and recurrent stroke (pHR including 10,429 patients: 1.50, 1.18–1.91, I2 = 0), however, not with mortality (pHR including 9,378 patients, 1.82, 0.73–4.57, I2 = 78%). Insulin resistance was associated with recurrent stroke (pHR including 21,363 patients: 1.56, 1.19–2.05, I2 = 55%), but not with mortality (pHR including 21,363 patients: 1.31, 0.66–2.59, I2 = 85%). Discussion: DM is associated with a 56% increased relative risk of death after IS and TIA. Risk estimates regarding recurrent events are similarly high between prediabetes and DM, indicating high cardiovascular risk burden already in precursor stages of DM. There was a high heterogeneity across most outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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21. The role of metabolic reprogramming in immune escape of triple-negative breast cancer.
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Ruochen Bao, Hongtao Qu, Baifeng Li, Kai Cheng, Yandong Miao, and Jiangtao Wang
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AMINO acid metabolism ,TRIPLE-negative breast cancer ,METABOLIC reprogramming ,LIPID metabolism ,CANCER relapse - Abstract
Triple-negative breast cancer (TNBC) has become a thorny problem in the treatment of breast cancer because of its high invasiveness, metastasis and recurrence. Although immunotherapy has made important progress in TNBC, immune escape caused by many factors, especially metabolic reprogramming, is still the bottleneck of TNBC immunotherapy. Regrettably, the mechanisms responsible for immune escape remain poorly understood. Exploring the mechanism of TNBC immune escape at the metabolic level provides a target and direction for follow-up targeting or immunotherapy. In this review, we focus on the mechanism that TNBC affects immune cells and interstitial cells through hypoxia, glucose metabolism, lipid metabolism and amino acid metabolism, and changes tumor metabolism and tumor microenvironment. This will help to find new targets and strategies for TNBC immunotherapy. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Excitation–contraction coupling reflects the metabolic profile of mantle muscle in young cuttlefish (Sepia officinalis)
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Callaghan, Neal I., Ducros, Loïck, Bennett, J. Craig, Capaz, Juan C., Andrade, José Pedro, Sykes, Antonio V., Driedzic, William R., Lamarre, Simon G., and MacCormack, Tyson J.
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SARCOPLASMIC reticulum , *CITRATE synthase , *MUSCLE metabolism , *GLUCOSE metabolism , *TRANSMISSION electron microscopy , *OXYGEN consumption - Abstract
The mantle muscle of common cuttlefish, Sepia officinalis, is responsible both for high‐magnitude and rapid movements for locomotion, as well as sustained ventilation, which require specific metabolic, electrophysiological, and structural organization. Young cuttlefish have a highly oxidative phenotype and a rapid growth rate. Here, we show high rates of oxygen consumption and protein synthesis in juveniles, and these rates decay exponentially over the first few weeks of growth. This is associated with considerable citrate synthase activity (relative to larger cuttlefish) but a lack of glucose metabolism based on zero uptake of glucose by isolated muscle sheets and minimal activity of hexokinase (similar to larger animals). In contrast to glucose metabolism in the heart, glucose metabolism in these muscle sheets was not stimulated by extracellular taurine. Previous research revealed an unusual ion channel complement in mantle myocytes, the most notable feature of which is the lack of a Na+ current during depolarization. Because this adaptation is not consistent across the coleoid clade, we investigated excitation–contraction coupling. Here, mantle energetics and contractility, including the individual components of the total Ca2+ flux driving contraction, were studied. Results indicate that the majority of Ca2+ current underlying contractile stress development capacity in cuttlefish juveniles is not mediated by dihydropyridine‐sensitive L‐type channels, in contrast to their adult counterparts, and the sarcoplasmic reticulum contributes little to routine contractility. We had previously noted an influence of physiological levels of taurine in limiting cardiac contractility but found no analogous sensitivity in mantle muscle. Finally, transmission electron microscopy of subcellular architecture revealed the presence of sarcoplasmic tubular aggregates, suggesting that oxidative inhibition of sarcoplasmic reticulum function limits its role in this life stage. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Molecular mechanisms regulating glucose metabolism in quinoa (Chenopodium quinoa Willd.) seeds under drought stress.
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Wang, Chunmei, Lu, Chuan, Wang, Junling, Liu, Xiaoqing, Wei, Zhimin, Qin, Yan, Zhang, Huilong, Wang, Xiaoxia, Wei, Boxiang, Lv, Wei, and Mu, Guojun
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CARBOHYDRATE metabolism , *GLUCOSE metabolism , *CROP yields , *ABIOTIC stress , *CITRIC acid , *QUINOA , *DROUGHT tolerance - Abstract
Background: Abiotic stress seriously affects the growth and yield of crops. It is necessary to search and utilize novel abiotic stress resistant genes for 2.0 breeding programme in quinoa. In this study, the impact of drought stress on glucose metabolism were investigated through transcriptomic and metabolomic analyses in quinoa seeds. Candidate drought tolerance genes on glucose metabolism pathway were verified by qRT-PCR combined with yeast expression system. Results: From 70 quinoa germplasms, drought tolerant material M059 and drought sensitive material M024 were selected by comprehensive evaluation of drought resistance. 7042 differentially expressed genes (DEGs) were indentified through transcriptomic analyses. Gene Ontology (GO) analysis revealed that these DEGs were closely related to carbohydrate metabolic process, phosphorus-containing groups, and intracellular membrane-bounded organelles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis detected that DEGs were related to pathways involving carbohydrate metabolisms, glycolysis and gluconeogenesis. Twelve key differentially accumulated metabolites (DAMs), (D-galactose, UDP-glucose, succinate, inositol, D-galactose, D-fructose-6-phosphate, D-glucose-6-phosphate, D-glucose-1-phosphate, dihydroxyacetone phosphate, ribulose-5-phosphate, citric acid and L-malate), and ten key candidate DEGs (CqAGAL2, CqINV, CqFrK7, CqCELB, Cqbg1x, CqFBP, CqALDO, CqPGM, CqIDH3, and CqSDH) involved in drought response were identified. CqSDH, CqAGAL2, and Cqβ-GAL13 were candidate genes that have been validated in both transcriptomics and yeast expression screen system. Conclusion: These findings provide a foundation for elucidating the molecular regulatory mechanisms governing glucose metabolism in quinoa seeds under drought stress, providing insights for future research exploring responses to drought stress in quinoa. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Chronic β3‐AR stimulation activates distinct thermogenic mechanisms in brown and white adipose tissue and improves systemic metabolism in aged mice.
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Natarajan, Duraipandy, Plakkot, Bhuvana, Tiwari, Kritika, Ekambaram, Shoba, Wang, Weidong, Rudolph, Michael, Mohammad, Mahmoud A., Chacko, Shaji K., Subramanian, Madhan, Tarantini, Stefano, Yabluchanskiy, Andriy, Ungvari, Zoltan, Csiszar, Anna, and Balasubramanian, Priya
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WHITE adipose tissue , *FATTY acid oxidation , *BROWN adipose tissue , *METABOLIC disorders , *ADRENERGIC agonists - Abstract
Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle‐aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age‐related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3‐adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18‐month‐old) C57BL/6JN mice. Sustained β3‐AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a favorable adipokine profile. At the cellular level, CL treatment increased uncoupling protein 1 (UCP1)‐dependent thermogenesis in brown adipose tissue (BAT). However, in white adipose tissue (WAT) depots, CL treatment increased glycerol and lipid de novo lipogenesis (DNL) and turnover suggesting the activation of the futile substrate cycle of lipolysis and reesterification in a UCP1‐independent manner. Increased lipid turnover was also associated with the simultaneous upregulation of proteins involved in glycerol metabolism, fatty acid oxidation, and reesterification in WAT. Further, a dose‐dependent impact of CL treatment on inflammation was observed, particularly in subcutaneous WAT, suggesting a potential mismatch between fatty acid supply and oxidation. These findings indicate that chronic β3‐AR stimulation activates distinct cellular mechanisms that increase energy expenditure in BAT and WAT to improve systemic metabolism in aged mice. Considering that people lose BAT with aging, activation of futile lipid cycling in WAT presents a novel strategy for improving age‐related metabolic dysfunction. [ABSTRACT FROM AUTHOR]
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- 2024
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25. The deubiquitinase USP15 drives malignant progression of gastric cancer through glucose metabolism remodeling.
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Huangfu, Longtao, Zhu, Huanbo, Wang, Gangjian, Chen, Junbing, Wang, Yongqi, Fan, Biao, Wang, Xiaoyang, Yao, Qian, Guo, Ting, Han, Jing, Hu, Ying, Du, Hong, Li, Xiaomei, Ji, Jiafu, and Xing, Xiaofang
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DEUBIQUITINATING enzymes , *GLUCOSE metabolism , *CARRIER proteins , *BIOCHEMICAL substrates , *STOMACH cancer - Abstract
Background: Ubiquitin-specific protease 15 (USP15) exhibits amplifications in various tumors, including gastric cancer (GC), yet its biological function and mechanisms in GC progression remain elusive. Methods: Here, we established stable USP15 knockdown or overexpression GC cell lines and explored the potential mechanism of USP15 in GC. Besides, we also identified interacting targets of USP15. Results: USP15 knockdown significantly impeded cell proliferation, invasion, epithelial-mesenchymal transition, and distal colonization in xenograft models, while enhancing oxaliplatin's antitumor effect. USP15 was involved in ubiquitination modification of glycolytic regulators. Silencing of USP15 suppressed glycolytic activity and impaired mitochondrial functions. Interference with USP15 expression reversed tumor progression and distal colonization in vivo. HKDC1 and IGF2BP3 were found as core interacting targets of USP15, and HKDC1 was identified as a substrate for ubiquitination modification by USP15, whereby USP15 regulated glucose metabolism activity by inhibiting the ubiquitination degradation of HKDC1. Conclusions: Our study unveiled aberrantly high expression of USP15 in GC tissues, correlating with malignant progression and nonresponse to neoadjuvant therapy. USP15 inhibitors, if developed, could be effective in promoting chemotherapy through glucose metabolism remodeling. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Effect of circadian clock disruption on type 2 diabetes.
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Hong Thuan Tran, Takeru Kondo, Ashry, Amal, Yunyu Fu, Hiroko Okawa, Sawangmake, Chenphop, and Hiroshi Egusa
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TYPE 2 diabetes ,INSULIN sensitivity ,INSULIN resistance ,GLUCOSE metabolism ,HYPOTHALAMIC-pituitary-adrenal axis - Abstract
Introduction: Type 2 diabetes (T2D) is the predominant form of diabetes mellitus and is among the leading causes of death with an increasing prevalence worldwide. However, the pathological mechanism underlying T2D remains complex and unclear. An increasing number of studies have suggested an association between circadian clock disruption and high T2D prevalence. Method: This review explores the physiological and genetic evidence underlying T2D symptoms associated with circadian clock disturbances, including insulin secretion and glucose metabolism. Results and Discussion: Notably, circadian clock disruption reduces insulin secretion and insulin sensitivity and negatively affects glucose homeostasis. The circadian clock regulates the hypothalamic-pituitary-adrenal axis, an important factor that regulates glucose metabolism and influences T2D progression. Therefore, circadian clock regulation is an attractive, novel therapeutic approach for T2D, and various circadian clock stabilizers play therapeutic roles in T2D. Lastly, this review suggests novel therapeutic and preventive approaches using circadian clock regulators for T2D. [ABSTRACT FROM AUTHOR]
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- 2024
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27. An isotopically-labelled temporal mass spectrometry imaging data analysis workflow to reveal glucose spatial metabolism patterns in bovine lens tissue.
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Shi, Dingchang, Grey, Angus C., and Guo, George
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GLUCOSE metabolism , *MASS spectrometry , *IMAGE analysis , *WORKFLOW management systems , *DATA analysis , *BIOLOGICAL systems - Abstract
Application of stable isotopically labelled (SIL) molecules in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) over a series of time points allows the temporal and spatial dynamics of biochemical reactions to be tracked in a biological system. However, these large kinetic MSI datasets and the inherent variability of biological replicates presents significant challenges to the rapid analysis of the data. In addition, manual annotation of downstream SIL metabolites involves human input to carefully analyse the data based on prior knowledge and personal expertise. To overcome these challenges to the analysis of spatiotemporal MALDI-MSI data and improve the efficiency of SIL metabolite identification, a bioinformatics pipeline has been developed and demonstrated by analysing normal bovine lens glucose metabolism as a model system. The pipeline consists of spatial alignment to mitigate the impact of sample variability and ensure spatial comparability of the temporal data, dimensionality reduction to rapidly map regional metabolic distinctions within the tissue, and metabolite annotation coupled with pathway enrichment modules to summarise and display the metabolic pathways induced by the treatment. This pipeline will be valuable for the spatial metabolomics community to analyse kinetic MALDI-MSI datasets, enabling rapid characterisation of spatio-temporal metabolic patterns from tissues of interest. [ABSTRACT FROM AUTHOR]
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- 2024
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28. The Synergistic Effects of Polyol Pathway-Induced Oxidative and Osmotic Stress in the Aetiology of Diabetic Cataracts.
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Thorne, Courtney A., Grey, Angus C., Lim, Julie C., and Donaldson, Paul J.
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LABORATORY rats , *CRYSTALLINE lens , *OXIDATIVE stress , *GLUCOSE metabolism , *PHYSIOLOGICAL adaptation - Abstract
Cataracts are the world's leading cause of blindness, and diabetes is the second leading risk factor for cataracts after old age. Despite this, no preventative treatment exists for cataracts. The altered metabolism of excess glucose during hyperglycaemia is known to be the underlying cause of diabetic cataractogenesis, resulting in localised disruptions to fibre cell morphology and cell swelling in the outer cortex of the lens. In rat models of diabetic cataracts, this damage has been shown to result from osmotic stress and oxidative stress due to the accumulation of intracellular sorbitol, the depletion of NADPH which is used to regenerate glutathione, and the generation of fructose metabolites via the polyol pathway. However, differences in lens physiology and the metabolism of glucose in the lenses of different species have prevented the translation of successful treatments in animal models into effective treatments in humans. Here, we review the stresses that arise from hyperglycaemic glucose metabolism and link these to the regionally distinct metabolic and physiological adaptations in the lens that are vulnerable to these stressors, highlighting the evidence that chronic oxidative stress together with osmotic stress underlies the aetiology of human diabetic cortical cataracts. With this information, we also highlight fundamental gaps in the knowledge that could help to inform new avenues of research if effective anti-diabetic cataract therapies are to be developed in the future. [ABSTRACT FROM AUTHOR]
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- 2024
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29. High-Protein Mulberry Leaves Improve Glucose and Lipid Metabolism via Activation of the PI3K/Akt/PPARα/CPT-1 Pathway.
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Shan, Ziyi, Zhang, Huilin, He, Changhao, An, Yongcheng, Huang, Yan, Fu, Wanxin, Wang, Menglu, Du, Yuhang, Xie, Jiamei, Yang, Yang, and Zhao, Baosheng
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HDL cholesterol , *LDL cholesterol , *LIPID metabolism , *GENE expression , *GLUCOSE metabolism , *ASPARTATE aminotransferase - Abstract
High-Protein Mulberry is a novel strain of mulberry. High-Protein Mulberry leaves (HPM) were the subject of this study, which aimed to investigate its efficacy and underlying mechanisms in modulating glucose and lipid metabolism. A six-week intervention using db/db mice was carried out to assess the effects of HPM on serum lipid levels, liver function, and insulin (INS) levels. qRT-PCR and Western Blotting were employed to measure key RNA and protein expressions in the PI3K/Akt and PPARα/CPT-1 pathways. UHPLC-MS and the Kjeldahl method were utilized to analyze the component content and total protein. Additionally, network pharmacology was employed to predict regulatory mechanism differences between HPM and Traditional Mulberry leaves. The results of the study revealed significant improvements in fasting blood glucose, glucose tolerance, and insulin resistance in mice treated with HPM. HPM notably reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and INS, while increasing high-density lipoprotein cholesterol (HDL-C) levels. The treatment also effectively mitigated liver fatty lesions, inflammatory infiltration, and islet atrophy. HPM activation of the PI3K/Akt/PPARα/CPT-1 pathway suggested its pivotal role in the regulation of glucose and lipid metabolism. With its rich composition and pharmacodynamic material basis, HPM displayed a greater number of targets associated with glucose and lipid metabolism pathways, underscoring the need for further research into its potential therapeutic applications. [ABSTRACT FROM AUTHOR]
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- 2024
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30. The Influence of the Protozoan Giardia lamblia on the Modulation of the Immune System and Alterations in Host Glucose and Lipid Metabolism.
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Klimczak, Sylwia, Packi, Kacper, Rudek, Alicja, Wenclewska, Sylwia, Kurowski, Marcin, Kurczabińska, Daniela, and Śliwińska, Agnieszka
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INTESTINAL barrier function , *METABOLIC disorders , *GLUCOSE metabolism , *GIARDIA lamblia , *INSULIN resistance - Abstract
Giardia lamblia, the cause of giardiasis, significantly impacts patients with metabolic disorders related to insulin resistance (IR). Both giardiasis and metabolic disorders share elements such as chronic inflammation and intestinal dysbiosis, which substantially affect the metabolic and cytokine profiles of patients. This review discusses the mechanisms of virulence of G. lamblia, its influence on the immune system, and its association with metabolic disorders. The review aims to show how G. lamblia invasion acts on the immune system and the glucose and lipid metabolism. Key findings reveal that G. lamblia infection, by disrupting intestinal permeability, alters microbiota composition and immune responses, potentially impairing metabolic status. Future research should focus on elucidating the specific mechanisms by which G. lamblia influences the metabolism, exploring the long-term consequences of chronic infection, and developing targeted therapeutic strategies that include both parasitic and metabolic aspects. These insights underscore the need for a multidisciplinary approach to the treatment of giardiasis in patients with metabolic disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Greater molecular potential for glucose metabolism in adipose tissue and skeletal muscle of women compared with men.
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Nicolaisen, Trine S., Sjøberg, Kim A., Carl, Christian S., Richter, Erik A., Kiens, Bente, Fritzen, Andreas M., and Lundsgaard, Anne‐Marie
- Abstract
Women typically have less muscle mass and more fat mass than men, while at the same time possessing similar or even greater whole‐body insulin sensitivity. Our study aimed to investigate the molecular factors in primarily adipose tissue, but also in skeletal muscle, contributing to this sex difference. In healthy, moderately active premenopausal women and men with normal weight (28 ± 5 and 23 ± 3 years old; BMI 22.2 ± 1.9 and 23.7 ± 1.7) and in healthy, recreationally active women and men with overweight (32.2 ± 6 and 31.0 ± 5 years old; BMI 29.8 ± 4.3 & 30.9 ± 3.7) matched at age, BMI, and fitness level, we assessed insulin sensitivity and glucose tolerance with a hyperinsulinemic–euglycemic clamp or oral glucose tolerance test and studied subcutaneous adipose tissue and skeletal muscle samples with western blotting. Additionally, we traced glucose‐stimulated glucose disposal in adipose tissues of female and male C57BL/6J littermate mice aged 16 weeks and measured glucose metabolic proteins. Our findings revealed greater protein expression related to glucose disposal in the subcutaneous adipose tissue (AKT2, insulin receptor, glucose transport 4) and skeletal muscle (hexokinase II, pyruvate dehydrogenase) in women compared to matched men with normal weight and with overweight. This increased protein capacity for glucose uptake extended to white adipose tissues of mice accompanied with ~2‐fold greater glucose uptake compared to male mice. Furthermore, even in the obese state, women displayed better glucose tolerance than matched men, despite having 46% body fat and 20 kg less lean mass. In conclusion, our findings suggest that the superior potential for glucose disposal in female subcutaneous adipose tissue and skeletal muscle, driven by greater expression of various glucose metabolic proteins, compensates for their lower muscle mass. This likely explains women's superior glucose tolerance and tissue insulin sensitivity compared to men. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Disruption of insulin receptor substrate 2 (IRS2) causes non-obese type 2 diabetes with β-cell dysfunction in the golden (Syrian) hamster.
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Hirose, Michiko, Inoue, Kimiko, Matoba, Shogo, Tatebe, Takaki, Tokita, Syun, Dodo, Yukiko, Tomishima, Toshiko, Hasegawa, Ayumi, Honda, Arata, Ozaki, Mao, Shinogi, Akiko, Yanagisawa, Ryoko, Fauzi, Muhammad, Murakami, Takaaki, Inagaki, Nobuya, Tamura, Masaru, and Ogura, Atsuo
- Subjects
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TYPE 2 diabetes , *GENE knockout , *GLUCOSE metabolism , *HAMSTERS , *METABOLIC models - Abstract
Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin levels upon glucose administration and showed β-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamster provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with β-cell dysfunction, the most common type of T2D in East Asian countries, including Japan. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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33. Investigating a New Way to Assess Metabolic Risk in Pregnant Females with Prior RYGB Surgery.
- Author
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Gisinger, Teresa, Reiter, Birgit, Preindl, Karin, Stimpfl, Thomas, Gard, Liliana-Imi, Baumgartner-Parzer, Sabina, Kautzky-Willer, Alexandra, and Leutner, Michael
- Abstract
Background: Obesity in pregnancy is linked to adverse clinical outcomes such as gestational diabetes. Recently, a risk score calculated by different ceramide concentrations was recognized as a new way to investigate cardiovascular risk. The aim was to analyze if the ceramide risk score and cardiometabolic risk vary between normal-weight, obese, and females with prior Roux-en-Y bypass surgery (RYGB) during pregnancy. Methods: Three cohorts were investigated: first, 25 pregnant females with a history of RYGB; second, 19 with preconception BMI ≥ 35 kg/m
2 ; and third, 19 normal-weight (preconception BMI < 25 kg/m2 ). Around the 24th to 28th weeks of gestation routine laboratory assessments, 3 h 75 g oral and intravenous glucose tolerance tests were carried out. The correlation of ceramide risk scores and ceramide ratios (Cer(d18:1/18:0)/Cer(d18:1/16:0)) with metabolic parameters was analyzed via Pearson correlation. The cohorts were compared via ANOVA and unpaired t-tests. Results: The RYGB cohort had lower ceramide risk scores and ratios compared to obese pregnant females (7.42 vs. 9.34, p = 0.025; 0.33 vs. 0.47, p < 0.001). Ceramide risk score and ratio were found to correlate negatively with insulin sensitivity (measured with the Matsuda (r = −0.376, p = 0.031; r = −0.455, p = 0.008) and calculated sensitivity index (r = −0.358, p = 0.044; r = −0.621, p < 0.001) in females without RYGB. The ceramide risk score correlated positively with body fat in RYGB females (r = 0.650, p = 0.012). Conclusions: We found that females after RYGB have lower ceramide risk scores and ceramide ratios compared to obese pregnant females, possibly indicating lower metabolic risk. [ABSTRACT FROM AUTHOR]- Published
- 2024
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34. Comparison of Glucose Metabolizing Properties of Enterobacterial Probiotic Strains In Vitro.
- Author
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Balanche, Jules, Lahaye, Emilie, Bremard, Lisa, Thomas, Benjamin, and Fetissov, Sergueï O.
- Abstract
Before the absorption in the intestine, glucose encounters gut bacteria, which may serve as a barrier against hyperglycemia by metabolizing glucose. In the present study, we compared the capacity of enterobacterial strains to lower glucose levels in an in vitro model of nutrient-induced bacterial growth. Two probiotic strains, Hafnia alvei HA4597 (H. alvei) and Escherichia coli (E. coli) Nissle 1917, as well as E. coli K12, were studied. To mimic bacterial growth in the gut, a planktonic culture was supplemented twice daily by the Luria Bertani milieu with or without 0.5% glucose. Repeated nutrient provision resulted in the incremental growth of bacteria. However, in the presence of glucose, the maximal growth of both strains of E. coli but not of H. alvei was inhibited. When glucose was added to the culture medium, a continuous decrease in its concentration was observed during each feeding phase. At its highest density, H. alvei displayed more efficient glucose consumption accompanied by a more pronounced downregulation of glucose transporters' expression than E. coli K12. Thus, the study reveals that the probiotic strain H. alvei HA4597 is more resilient to maintain its growth than E. coli in the presence of 0.5% glucose accompanied by more efficient glucose consumption. This experimental approach offers a new strategy for the identification of probiotics with increased glucose metabolizing capacities potentially useful for the prevention and co-treatment of type 2 diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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35. Twenty-Four Hour Glucose Profiles and Glycemic Variability during Intermittent Religious Dry Fasting and Time-Restricted Eating in Subjects without Diabetes: A Preliminary Study.
- Author
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Peters, Beeke, Pappe, Christina Laetitia, Koppold, Daniela A., Schipp, Katharina, Arnrich, Bert, Michalsen, Andreas, Dommisch, Henrik, Steckhan, Nico, and Pivovarova-Ramich, Olga
- Abstract
Intermittent religious fasting increases the risk of hypo- and hyperglycemia in individuals with diabetes, but its impact on those without diabetes has been poorly investigated. The aim of this preliminary study was to examine the effects of religious Bahá'í fasting (BF) on glycemic control and variability and compare these effects with time-restricted eating (TRE). In a three-arm randomized controlled trial, 16 subjects without diabetes were assigned to a BF, TRE, or control group. Continuous glucose monitoring and food intake documentation were conducted before and during the 19 days of the intervention, and the 24 h mean glucose and glycemic variability indices were assessed. The BF and TRE groups, but not the control group, markedly reduced the daily eating window while maintaining macronutrient composition. Only the BF group decreased caloric intake (−677.8 ± 357.6 kcal, p = 0.013), body weight (−1.92 ± 0.95 kg, p = 0.011), and BMI (−0.65 ± 0.28 kg, p = 0.006). Higher maximum glucose values were observed during BF in the within-group (+1.41 ± 1.04, p = 0.039) and between-group comparisons (BF vs. control: p = 0.010; TRE vs. BF: p = 0.022). However, there were no alterations of the 24 h mean glucose, intra- and inter-day glycemic variability indices in any group. The proportions of time above and below the range (70–180 mg/dL) remained unchanged. BF and TRE do not exhibit negative effects on glycemic control and variability in subjects without diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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36. Research Progress on Metabolic Regulation Function and Its Applications of Polygonatum.
- Author
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ZHANG Yan, TU Wen, WANG Shuzhen, and WU Wei
- Subjects
METABOLIC regulation ,BLOOD sugar ,LIPID metabolism ,INDUSTRIALIZATION ,GLUCOSE metabolism - Abstract
Polygonatum sibiricum, a plant homologous to both medicine and food, is of significant importance. Its primary active components include polysaccharides, saponin, flavonoids, polyphenols, and alkaloids. These constituents are known for their roles in enhancing immune function, combating fatigue, providing anti-oxidative benefits, reducing blood sugar, and offering anti-inflammatory effects. Consequently, P. sibiricum presents wide-ranging prospects in health food and pharmaceutical research and development. This paper provides a comprehensive summary of research advancements in the polysaccharides, flavonoids, saponins, and solomonseal rhizome extract of P. sibiricum, particularly in metabolic regulation. It delves into the mechanisms by which the main active substances of P. sibiricum influence glucose and lipid metabolism. Simultaneously, the paper analyzes current patents and the state of industrial development related to P. sibiricum, aiming to provide a reference for future research and development of metabolic regulation functional products based on this plant. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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37. Effect of Berberis dasystachya Polysaccharide on Glucose and Lipid Metabolisms in STZ-induced Type I Diabetic Rats.
- Author
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MA Nana, HAN Lijuan, YANG Yongjing, SUO Yourui, YUAN Zhenzhen, and YE Ying
- Subjects
POLYSACCHARIDES ,LABORATORY rats ,GLUCOSE metabolism ,BLOOD sugar ,LIPID metabolism - Abstract
In order to provide theoretical support for diabetes prevention and therapy, this study investigated the regulatory effect of Berberis dasystachya Maxim. Polysaccharide (BDP) on glucose and lipid metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetic model rats were randomly assigned to the model control group, low-dose polysaccharide group (BDP-L, 10 mg/kg), mid-dose polysaccharide group (BDP-M, 200 mg/kg), and high-dose group (BDP-H, 400 mg/kg). Blood lipid levels, lipid metabolic enzyme activity, and antioxidant enzyme activity served as evaluation markers. Results showed that after 28 days of administering yellow thorn polysaccharide, the BDP-treated groups exhibited significantly (P<0.05) lower blood glucose and lipid levels compared to the model group, with a remarkable 39.16% reduction in blood glucose in the high-dose group (P<0.01). In contrast, serum insulin levels and hepatic glycogen (HG) levels increased in the BDP-treated groups (P<0.05 or P<0.01), with a 1.28-fold increase in serum insulin (P<0.01) and an 89.79% increase in HG (P<0.01) in the high-dose group. Furthermore, compared to the model group, serum and pancreatic levels of catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH-Px) were significantly elevated (P<0.05 or P<0.01), while malondialdehyde (MDA) levels were considerably reduced (P<0.05) in a dose-dependent manner following BDP treatment. In conclusion, BDP effectively improved glucolipid metabolism in diabetic rats by alleviating oxidative stress, ultimately safeguarding pancreatic β-cell integrity in type I diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
38. Oxytocin does not acutely improve glucose tolerance in men with type 2 diabetes.
- Author
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Goll, Nina, Moszka, Nina, Kantartzis, Konstantinos, Preissl, Hubert, Gruber, Tim, Fritsche, Louise, Jumpertz‐von Schwarzenberg, Reiner, García‐Cáceres, Cristina, Fritsche, Andreas, and Hallschmid, Manfred
- Subjects
- *
TYPE 2 diabetes , *GLUCOSE tolerance tests , *GLUCOSE metabolism , *INSULIN resistance , *BODY mass index , *INSULIN , *INSULIN sensitivity - Abstract
Aim Methods Results Conclusions To assess oxytocin's acute glucoregulatory impact in men with type 2 diabetes in the context of our previous findings that oxytocin improves β‐cell responsivity in healthy men.In a double‐blind, crossover comparison, intranasal oxytocin (24 IU) and placebo, respectively, were administered to 25 fasted men with non‐insulin–treated type 2 diabetes (age ± standard error of the mean, 63.40 ± 1.36 years; body mass index, 27.77 ± 0.66 kg/m2; HbA1c, 6.86% ± 0.08%; Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR, 3.44 ± 0.39) 60 minutes before an oral glucose tolerance test (oGTT). Key outcomes were compared with previous results in men with normal weight or obesity.Oxytocin compared with placebo increased plasma oxytocin concentrations and reduced the heart rate, but did not alter glucose metabolism in the 3 hours after oGTT onset (area under the curve, glucose, 2240 ± 80.5 vs. 2190 ± 69.5 mmol/L × min; insulin, 45 663 ± 4538 vs. 44 343 ± 4269 pmol/L × min; C‐peptide, 235 ± 5.1 vs. 231 ± 15.9 nmol/L × min).This outcome contrasts with the oxytocin‐induced attenuation of early postprandial glucose excursions in normal‐weight individuals, but is in line with the absence of respective effects in men with obesity. We conclude that insulin resistance in type 2 diabetes is associated with decreased sensitivity to the acute glucoregulatory effect of oxytocin in male individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. Huanshaodan regulates microglial glucose metabolism reprogramming to alleviate neuroinflammation in AD mice through mTOR/HIF-1α signaling pathway.
- Author
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Congcong Shang, Yunfang Su, Jinlian Ma, Zhonghua Li, Pan Wang, Huifen Ma, Junying Song, and Zhenqiang Zhang
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METABOLIC reprogramming ,GLUCOSE metabolism ,ALZHEIMER'S disease ,LACTATE dehydrogenase ,CLINICAL medicine - Abstract
Abnormal glucose metabolism in microglial is closely associated with Alzheimer's disease (AD). Reprogramming of microglial glucose metabolism is centered on regulating the way in which microglial metabolize glucose to alter microglial function. Therefore, reprogramming microglial glucose metabolism is considered as a therapeutic strategy for AD. Huanshaodan (HSD) is a Chinese herbal compound which shows significant efficacy in treating AD, however, the precise mechanism by which HSD treats AD remains unclear. This study is aim to investigate whether HSD exerts anti-AD effects by regulating the metabolic reprogramming of microglial through the mTOR/HIF-1α signaling pathway. SAMP8 mice and BV2 cells were used to explore the alleviative effect of HSD on AD and the molecular mechanism in vivo and in vitro. The pharmacodynamic effects of HSD was evaluated by behavioral tests. The pathological deposition of Aβ in brain of mice was detected by immunohistochemistry. ELISA method was used to measure the activity of HK2 and the expression of PKM2, IL-6 and TNF-α in hippocampus and cortex tissues of mice. Meanwhile, proteins levels of p-mTOR, mTOR, HIF-1α, CD86, Arg1 and IL-1β were detected by Western-blot. LPS-induced BV2 cells were treated with HSD-containing serum. The analysis of the expression profiles of the CD86 and CD206 markers by flow cytometry allows us to distinguish the BV2 polarization. Glucose, lactic acid, ATP, IL-6 and TNF-α levels, as well as lactate dehydrogenase and pyruvate dehydrogenase activities were evaluated in the BV2. Western-blot analysis was employed to detect mTOR, p-mTOR, HIF-1α and IL-1β levels in BV2. And the mTOR agonist MHY1485 (MHY) was chosen to reverse validate. In this study, it is found that HSD improved cognitive impairment in SAMP8 mice and reduced Aβ deposition, suppressed the levels of glycolysis and neuroinflammation in mice. In LPS-induced BV2 cells, HSD also regulated glycolysis and neuroinflammation, and suppressed the mTOR/HIF-1α signaling pathway. More importantly, these effects were reversed by MHY. It is demonstrated that HSD regulated microglial glucose metabolism reprogramming by inhibiting the mTOR/HIF-1α signaling pathway, alleviated neuroinflammation, and exerted anti-AD effects. This study provided scientific evidence for the clinical application of HSD for treating AD. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Human chemerin induces eryptosis at concentrations exceeding circulating levels.
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TKACHENKO, MARYNA, ONISHCHENKO, ANATOLII, TRYFONYUK, LILIYA, BUTOV, DMYTRO, KOT, KATERYNA, NOVIKOVA, VIKTORIIA, FAN, LIWEI, PROKOPIUK, VOLODYMYR, KOT, YURII, and TKACHENKO, ANTON
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CHEMERIN , *CALCIUM supplements , *ERYTHROCYTES , *REACTIVE nitrogen species , *REACTIVE oxygen species , *VITAMIN C , *CELL membranes , *GLUCOSE metabolism - Abstract
Introduction: Human chemerin is an adipokine that regulates chemotaxis, inflammation, and glucose metabolism. In addition, accumulating evidence suggests that chemerin promotes apoptosis, autophagy, and pyroptosis. However, there are no data on its impact on eryptosis. The current study aimed to analyze the effects of human active Glu-Ser chemerin on eryptosis in vitro. Materials and Methods: Human chemerin 0-2-10-50 µg/mL was incubated for 24 h with human erythrocytes (hematocrit 0.4%) obtained from eight healthy individuals. Flow cytometry-based determination of phospholipid scrambling, reactive oxygen species (ROS) production, and intracellular Ca levels was performed. To supplement data on ROS and Ca signaling in chemerin-mediated eryptosis, incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca-binding agent EGTA was carried out, respectively. Confocal microscopy-based techniques were used to detect reactive nitrogen species (RNS) generation, involvement of caspase-3 and caspase-8, as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu-Ser chemerin. Results: Our observations suggest that human Glu-Ser chemerin had no impact on eryptosis parameters at 2 µg/mL. However, chemerin stimulated phosphatidylserine externalization, ROS production, and Ca accumulation at higher concentrations suggesting activation of eryptosis. Ca uptake turned out to be at least partly required for chemerin-mediated eryptosis. Chemerin-mediated erythrotoxicity was additionally mediated by RNS, caspase-3, and caspase-8. Moreover, Glu-Ser chemerin promoted reduction in the liquid-ordered phase of cell membranes in erythrocytes. Conclusions: The present study first discloses that human chemerin can induce eryptosis via Ca-dependent mechanisms at concentrations noticeably exceeding circulating levels. Thus, chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in diseases associated with enhanced levels of chemerin in blood. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Organic carbon utilisation by the filamentous alga Tribonema.
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Liu, Jiajun, Crosbie, Nicholas D., Scales, Peter J., and Martin, Gregory J. O.
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Filamentous algae have potential application to wastewater treatment, in particular for efficient recovery of nutrients into biomass. However, supplying inorganic carbon is a major limiting factor. The utilisation of organic carbon present in wastewater may reduce the constraints in carbon supply, however there is little knowledge of mixotrophic growth amongst filamentous algae. This study investigated the utilisation of organic carbon sources relevant to wastewater by the filamentous xanthophyte alga Tribonema. Algae growth was compared in the absence of organic carbon (autotrophic) and in presence of 0.2 g-C L-1 glucose, ethanol or acetate under mixotrophic (presence of organic carbon and light) or heterotrophic (presence of organic carbon and absence of light) conditions. To investigate direct utilisation of organic carbon and indirect utilisation via bacterial CO2-genesis, cultivation was performed under both axenic and non-axenic conditions. Tribonema was found to directly utilise glucose, which increased mixotrophic productivity and maintained growth under heterotrophic conditions. In contrast, acetate was only indirectly utilised mixotrophically in the presence of bacteria, whereas ethanol was not utilised under any conditions. The underlying mechanisms of glucose utilisation by Tribonema were also investigated by analysing its photosynthetic rate and respiration rate under glucose concentrations ranging from 0 – 100 g L-1. Based on the results, enhancements to metabolic pathways and reduced CO2 requirements provided by glucose utilisation were proposed. Despite the positive results with respect to glucose utilisation, out competition for this resource by bacteria suggest that Tribonema is more suitable for treatment of wastewater with low organic carbon concentrations, such as secondary-treated wastewater effluent. [ABSTRACT FROM AUTHOR]
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- 2024
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42. Gut Microbiota in the Progression of Type 2 Diabetes and the Potential Role of Exercise: A Critical Review.
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Deli, Chariklia K., Fatouros, Ioannis G., Poulios, Athanasios, Liakou, Christina A., Draganidis, Dimitrios, Papanikolaou, Konstantinos, Rosvoglou, Anastasia, Gatsas, Athanasios, Georgakouli, Kalliopi, Tsimeas, Panagiotis, and Jamurtas, Athanasios Z.
- Abstract
Type 2 diabetes (T2D) is the predominant metabolic epidemic posing a major threat to global health. Growing evidence indicates that gut microbiota (GM) may critically influence the progression from normal glucose tolerance, to pre-diabetes, to T2D. On the other hand, regular exercise contributes to the prevention and/or treatment of the disease, and evidence suggests that a possible way regular exercise favorably affects T2D is by altering GM composition toward health-promoting bacteria. However, research regarding this potential effect of exercise-induced changes of GM on T2D and the associated mechanisms through which these effects are accomplished is limited. This review presents current data regarding the association of GM composition and T2D and the possible critical GM differentiation in the progression from normal glucose, to pre-diabetes, to T2D. Additionally, potential mechanisms through which GM may affect T2D are presented. The effect of exercise on GM composition and function on T2D progression is also discussed. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Decomposed FDG PET-based phenotypic heterogeneity predicting clinical prognosis and decision-making in temporal lobe epilepsy patients.
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Guo, Kun, Quan, Zhiyong, Li, Guiyu, Li, Baojuan, Kang, Fei, and Wang, Jing
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EPILEPSY , *TEMPORAL lobe epilepsy , *PEOPLE with epilepsy , *LATENT infection , *PROGNOSIS , *HETEROGENEITY - Abstract
Objective: This study utilized a data-driven Bayesian model to automatically identify distinct latent disease factors represented by overlapping glucose metabolism patterns from 18F-Fluorodeoxyglucose PET (18F-FDG PET) to analyze heterogeneity among patients with TLE. Methods: We employed unsupervised machine learning to estimate latent disease factors from 18F-FDG PET scans, representing whole-brain glucose metabolism patterns in seventy patients with TLE. We estimated the extent to which multiple distinct factors were expressed within each participant and analyzed their relevance to epilepsy burden, including seizure onset, duration, and frequency. Additionally, we established a predictive model for clinical prognosis and decision-making. Results: We identified three latent disease factors: hypometabolism in the unilateral temporal lobe and hippocampus (factor 1), hypometabolism in bilateral prefrontal lobes (factor 2), and hypometabolism in bilateral temporal lobes (factor 3), variably co-expressed within each patient. Factor 3 demonstrated the strongest negative correlation with the age of onset and duration (r = − 0.33, − 0.38 respectively, P < 0.05). The supervised classifier, trained on latent disease factors for predicting patient-specific antiepileptic drug (AED) responses, achieved an area under the curve (AUC) of 0.655. For post-surgical seizure outcomes, the AUC was 0.857, and for clinical decision-making, it was 0.965. Conclusions: Decomposing 18F-FDG PET-based phenotypic heterogeneity facilitates individual-level predictions relevant to disease monitoring and personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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44. Loss of Bcl‐3 regulates macrophage polarization by promoting macrophage glycolysis.
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Liu, Shengnan, Wang, Hao, Li, Jiaoyang, Gao, Jingtao, Yu, Li, Wei, Xiaofei, Cui, Mengchao, Zhao, Yuxin, Liang, Yinming, and Wang, Hui
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NF-kappa B , *LIPID metabolism , *GLUCOSE metabolism , *MACROPHAGES , *GLYCOLYSIS - Abstract
M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B‐cell lymphoma‐3 (Bcl‐3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl‐3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl‐3 in macrophages can regulate glycolysis‐related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl‐3 was able to promote the interferon gamma/lipopolysaccharide‐induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl‐3 may be a candidate gene for regulating M1 polarization in macrophages. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Cerebral glucose metabolic correlates of cognitive and behavioural impairments in amyotrophic lateral sclerosis.
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Lehto, Annaliis, Schumacher, Julia, Kasper, Elisabeth, Teipel, Stefan, Hermann, Andreas, Kurth, Jens, Krause, Bernd Joachim, and Prudlo, Johannes
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AMYOTROPHIC lateral sclerosis , *COGNITIVE testing , *POSITRON emission tomography , *GLUCOSE metabolism , *COGNITION - Abstract
Objective: Half of ALS patients are cognitively and/or behaviourally impaired. As cognition/behaviour and cerebral glucose metabolism can be correlated by means of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), we aimed to utilise FDG-PET, first, to replicate group-level differences in glucose metabolism between non-demented ALS patients separated into non-impaired (ALSni), cognitively impaired (ALSci), behaviourally impaired (ALSbi), and cognitively and behaviourally impaired (ALScbi) groups; second, to investigate glucose metabolism and performance in various cognitive domains; and third, to examine the impact of partial volume effects correction (PVEC) of the FDG-PET data on the results. Methods: We analysed neuropsychological, clinical, and imaging data from 67 ALS patients (30 ALSni, 21 ALSci, 5 ALSbi, and 11 ALScbi). Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen, and two social cognition tests. FDG-PET and structural MRI scans were acquired for each patient. Voxel-based statistical analyses were undertaken on grey matter volume (GMV) and non-corrected vs. PVE-corrected FDG-PET scans. Results: ALSci and ALScbi had lower cognitive scores than ALSni. In contrast to both ALSni and ALSci, ALScbi showed widespread hypometabolism in the superior- and middle-frontal gyri in addition to the right temporal pole. Correlations were observed between the GMV, the FDG-PET signal, and various cognitive scores. The FDG-PET results were largely unaffected by PVEC. Interpretation: Our study identified widespread differences in hypometabolism in the ALScbi-ni but not in the ALSci-ni group comparison, raising the possibility that cerebral metabolism may be more closely related to the presence of behavioural changes than to mild cognitive deficits. [ABSTRACT FROM AUTHOR]
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- 2024
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46. Exosome-Derived MicroRNA-221-3p Desensitizes Breast Cancer Cells to Adriamycin by Regulating PIK3r1-Mediated Glycose Metabolism.
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Hong, Xiaolu and Pan, Xiaoping
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FLOW cytometry , *DRUG resistance in cancer cells , *T-test (Statistics) , *DATA analysis , *RESEARCH funding , *BREAST tumors , *MICRORNA , *APOPTOSIS , *CELL proliferation , *QUANTITATIVE research , *REVERSE transcriptase polymerase chain reaction , *LACTATE dehydrogenase , *FLUORESCENT antibody technique , *CELL lines , *GENES , *BLOOD sugar , *GENE expression , *CELL culture , *DOXORUBICIN , *CYTOMETRY , *ONE-way analysis of variance , *STATISTICS , *EXOSOMES - Abstract
Background: Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of adriamycin resistance in breast cancer (BC) remains unclear. Methods: Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on adriamycin resistance. Results: Elevated levels of miR-221-3p expression were observed in adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in adriamycin-resistant cells. PIK3R1 was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of PIK3R1, p-AKT, c-Myc, HK2, and PKM2, decreased FOXO3 expression, and weakened the adriamycin resistance in resistant cells. Conclusions: miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target PIK3R1 and promoted adriamycin resistance in BC cells. [ABSTRACT FROM AUTHOR]
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- 2024
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47. Type 2 Diabetes Mellitus in Low- and Middle-Income Countries: The Significant Impact of Short-Chain Fatty Acids and Their Quantification.
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Khumalo, Scelo, Duma, Zamathombeni, Bekker, Lizette, Nkoana, Koketso, and Pheeha, Sara Mosima
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SHORT-chain fatty acids , *TYPE 2 diabetes , *MIDDLE-income countries , *DIETARY fiber , *GLUCOSE metabolism - Abstract
Globally, type 2 diabetes mellitus (T2DM) is a major threat to the public's health, particularly in low- and middle-income countries (LMICs). The production of short-chain fatty acids (SCFAs) by the gut microbiota has been reported to have the potential to reduce the prevalence of T2DM, particularly in LMICs where the disease is becoming more common. Dietary fibers are the primary source of SCFAs; they can be categorized as soluble (such as pectin and inulin) or insoluble (such as resistant starches). Increased consumption of processed carbohydrates, in conjunction with insufficient consumption of dietary fiber, has been identified as a significant risk factor for type 2 diabetes (T2DM). However, there are still controversies over the therapeutic advantages of SCFAs on human glucose homeostasis, due to a lack of studies in this area. Hence, a few questions need to be addressed to gain a better understanding of the beneficial link between SCFAs and glucose metabolism. These include the following: What are the biochemistry and biosynthesis of SCFAs? What role do SCFAs play in the pathology of T2DM? What is the most cost-effective strategy that can be employed by LMICs with limited laboratory resources to enhance their understanding of the beneficial function of SCFAs in patients with T2DM? To address the aforementioned questions, this paper aims to review the existing literature on the protective roles that SCFAs have in patients with T2DM. This paper further discusses possible cost-effective and accurate strategies to quantify SCFAs, which may be recommended for implementation by LMICs as preventive measures to lower the risk of T2DM. [ABSTRACT FROM AUTHOR]
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- 2024
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48. Exploring the active components and potential mechanisms of Alpiniae oxyphyllae Fructus in treating diabetes mellitus with depression by UPLC-Q-Exactive Orbitrap/MS, network pharmacology and molecular docking.
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Qi, Yue, Zhou, Qilun, Zhang, Yongping, Deng, Jinlan, Li, Ruonan, and Zhang, Xiaofeng
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MOLECULAR docking , *MOLECULAR pharmacology , *PROTEIN-protein interactions , *INSULIN resistance , *GLUCOSE metabolism - Abstract
The growing incidence of diabetes mellitus (DM) and depression is a global public health issue. Alpiniae oxyphyllae Fructus (AOF) is a kind of medicinal and edible plant which be found with anti-diabetic property, and could improve depression-like symptoms. This study aimed to screen active targets and potential mechanisms of AOF in treating DM with depression. Injection of streptozotocin (STZ) and exposure to chronic unpredictable mild stress (CUMS) for 4 weeks were used to conduct the DM with depression mice model. Behavioral tests, indexes of glucose metabolism, monoamine neurotransmitters, inflammatory cytokine and oxidative stress were measured. Histopathological change of hippocampus tissue was observing by HE and Nissl staining. UPLC-Q-Exactive Orbitrap/MS, network pharmacology and molecular docking were used to explore the chemical components and mechanisms of AOF on the DM with depression. AOF showed a reversed effect on body weight in DM with depression mice. Glucose metabolism and insulin resistance could be improved by treatment of AOF. In addition, AOF could alleviate depression-like behaviors based on the results of behavior tests and monoamine neurotransmitters. AOF also attenuated STZ-CUMS induced neuron injury in hippocampus. Next, a total of 61 chemical components were identified in the UPLC-Q-Exactive Orbitrap/MS analysis of the extract of AOF. Network pharmacology analysis suggested that 12 active components and 227 targets were screened from AOF, and 1802 target genes were screened from DM with depression, finally 126 intersection target genes were obtained. Drug-disease targets network was constructed and implied that the top five components with a higher degree value includes quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol. Protein-protein interaction (PPI) network showed that MAPK1, FOS, AKT1, IL6 and TP53 may be the core intersection targets. The mechanism of the effect of AOF on DM with depression was analyzed through gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, mainly involved in AGE/RAGE, PI3K/AKT, and MAPK signaling pathways. The results of molecular docking indicated that quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol all had good binding to the core intersection targets. Overall, our experimental researches have demonstrated that AOF could exert the dual effects of anti-diabetic and anti-depression on DM with depression mice, through multi-targets and multi-pathways. [ABSTRACT FROM AUTHOR]
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- 2024
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49. Whole grains-derived functional ingredients against hyperglycemia: targeting hepatic glucose metabolism.
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Wang, Yu, Fan, Mingcong, Qian, Haifeng, Ying, Hao, Li, Yan, and Wang, Li
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HOMEOSTASIS , *GLUCOSE metabolism , *TYPE 2 diabetes , *HYPERGLYCEMIA , *INSULIN resistance - Abstract
Type 2 diabetes mellitus (T2DM) is characterized by the dysregulation of glucose homeostasis, resulting in hyperglycemia. However, concerns have been raised about the safety and efficacy of current hypoglycemic drugs due to undesirable side effects. Increasing studies have shown that whole grains (WG) consumption is inversely associated with the risk of T2DM and its subsequent complications. Thus, dietary strategies involving functional components from the WG provide an intriguing approach to restoring and maintaining glucose homeostasis. This review provides a comprehensive understanding of the major functional components derived from WG and their positive effects on glucose homeostasis, demonstrates the underlying molecular mechanisms targeting hepatic glucose metabolism, and discusses the unclear aspects according to the latest viewpoints and current research. Improved glycemic response and insulin resistance were observed after consumption of WG-derived bioactive ingredients, which are involved in the integrated, multi-factorial, multi-targeted regulation of hepatic glucose metabolism. Promotion of glucose uptake, glycolysis, and glycogen synthesis pathways, while inhibition of gluconeogenesis, contributes to amelioration of abnormal hepatic glucose metabolism and insulin resistance by bioactive components. Hence, the development of WG-based functional food ingredients with potent hypoglycemic properties is necessary to manage insulin resistance and T2DM. [ABSTRACT FROM AUTHOR]
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- 2024
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50. Impact of irregular sleep pattern, and sleep quality on glycaemic parameters and endothelial function in adolescents and young adults with type 1 diabetes.
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Promsod, Ornpisa, Kositanurit, Weerapat, Tabtieang, Tanat, Kulaputana, Onanong, Chirakalwasan, Naricha, Reutrakul, Sirimon, and Sahakitrungruang, Taninee
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YOUNG adults , *SLEEP quality , *TYPE 1 diabetes , *CONTINUOUS glucose monitoring , *SLEEP duration , *INSULIN sensitivity , *SLEEP - Abstract
Summary: This study investigated the impact of comprehensive sleep patterns on glycaemic parameters and endothelial function in adolescents and young adults with type 1 diabetes (T1D). Thirty subjects with type 1 diabetes (aged 13–25) without chronic complications participated. For 1 week, glucose levels were monitored by real‐time continuous glucose monitoring (CGM) and sleep was simultaneously assessed by actigraphy. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Flow‐mediated dilatation (FMD) measured endothelial function at the brachial artery. Insulin sensitivity was determined by calculated estimated glucose disposal rate (eGDR). Glycaemic control was assessed using haemoglobin A1C (HbA1C) levels. To address potential confounding by metabolic syndrome on the FMD results, three affected subjects were excluded from FMD correlation analyses. Participants with PSQI scores >5 had a lower %FMD compared with those with scores ≤5 (4.6 ± 3.7% vs. 7.6 ± 3.0%, p = 0.03). Multivariate analysis indicated that lower sleep efficiency and higher sleep duration variability were associated with higher HbA1C levels (β = −0.076, 95%CI [−0.145, −0.008], p = 0.029; β = 0.012, 95%CI [0.001, 0.023], p = 0.033). Irregular sleep timing and lower sleep efficiency were related to decreased insulin sensitivity (sleep midpoint irregularity β = −1.581, 95%CI [−2.661, −0.502], p = 0.004, and sleep efficiency β = 0.147, 95%CI [0.060, 0.235], p = 0.001). No significant associations were found between glycaemic parameters and FMD. Our study demonstrated that sleep irregularity in type 1 diabetes was associated with glycaemic control and insulin resistance, while poor subjective sleep quality was linked to endothelial dysfunction. Promoting healthy sleep habits, including consistent sleep timing could benefit metabolic and cardiovascular health in type 1 diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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