scholarly journals Tetrahydrocurcumin Upregulates the Adiponectin-AdipoR Pathway and Improves Insulin Signaling and Pancreatic β-Cell Function in High-Fat Diet/Streptozotocin-Induced Diabetic Obese Mice

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4552
Author(s):  
Yi-Zhen Tsai ◽  
Mei-Ling Tsai ◽  
Li-Yin Hsu ◽  
Chi-Tang Ho ◽  
Ching-Shu Lai
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Cell Function ◽  
Obese Mice ◽  
High Fat ◽  
Islet Mass ◽  
Beneficial Effects ◽  
Β Cell Function

Impairment of adiponectin production and function is closely associated with insulin resistance and type 2 diabetes, which are linked to obesity. Studies in animal models have documented the anti-diabetic effects of tetrahydrocurcumin (THC). Although several possible mechanisms have been proposed, the contribution of adiponectin signaling on THC-mediated antihyperglycemic effects remains unknown. Here, we report that adiposity, steatosis, and hyperglycemia were potently attenuated in high-fat diet/streptozotocin-induced diabetic obese mice after they received 20 and 100 mg/kg THC for 14 weeks. THC upregulated UCP-1 in adipose tissue and elevated adiponectin levels in the circulation. THC upregulated the AdipoR1/R2-APPL1-mediated pathway in the liver and skeletal muscle, which contributes to improved insulin signaling, glucose utilization, and lipid metabolism. Furthermore, THC treatment significantly (p < 0.05) preserved islet mass, reduced apoptosis, and restored defective insulin expression in the pancreatic β-cells of diabetic obese mice, which was accompanied by an elevation of AdipoR1 and APPL1. These results demonstrated a potential mechanism underlying the beneficial effects of THC against hyperglycemia via the adiponectin-AdipoR pathway, and thus, may lead to a novel therapeutic use for type 2 diabetes.

scholarly journals Leptin restores the insulinotropic effect of exenatide in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet

2014 ◽  
Vol 307 (8) ◽  
pp. E712-E719 ◽  
Author(s):  
Takeru Sakai ◽  
Toru Kusakabe ◽  
Ken Ebihara ◽  
Daisuke Aotani ◽  
Sachiko Yamamoto-Kataoka ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Triglyceride Level ◽  
High Fat Diet ◽  
Receptor Agonist ◽  
Cell Function ◽  
High Fat ◽  
Β Cell ◽  
Β Cell Function ◽  
Insulinotropic Effect

Leptin may reduce pancreatic lipid deposition, which increases with progression of obesity and can impair β-cell function. The insulinotropic effect of glucagon-like peptide-1 (GLP-1) and the efficacy of GLP-1 receptor agonist are reduced associated with impaired β-cell function. In this study, we examined whether leptin could restore the efficacy of exenatide, a GLP-1 receptor agonist, in type 2 diabetes with increased adiposity. We chronically administered leptin (500 μg·kg−1·day−1) and/or exenatide (20 μg·kg−1·day−1) for 2 wk in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet (STZ/HFD mice). The STZ/HFD mice exhibited hyperglycemia, overweight, increased pancreatic triglyceride level, and reduced glucose-stimulated insulin secretion (GSIS); moreover, the insulinotropic effect of exenatide was reduced. However, leptin significantly reduced pancreatic triglyceride level, and adding leptin to exenatide (LEP/EX) remarkably enhanced GSIS. These results suggested that the leptin treatment restored the insulinotropic effect of exenatide in the mice. In addition, LEP/EX reduced food intake, body weight, and triglyceride levels in the skeletal muscle and liver, and corrected hyperglycemia to a greater extent than either monotherapy. The pair-feeding experiment indicated that the marked reduction of pancreatic triglyceride level and enhancement of GSIS by LEP/EX occurred via mechanisms other than calorie restriction. These results suggest that leptin treatment may restore the insulinotropic effect of exenatide associated with the reduction of pancreatic lipid deposition in type 2 diabetes with increased adiposity. Combination therapy with leptin and exenatide could be an effective treatment for patients with type 2 diabetes with increased adiposity.

scholarly journals Baicalein Protects against Type 2 Diabetes via Promoting Isletβ-Cell Function in Obese Diabetic Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Yu Fu ◽  
Jing Luo ◽  
Zhenquan Jia ◽  
Wei Zhen ◽  
Kequan Zhou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Cell Function ◽  
Diabetic Mice ◽  
Obese Mice ◽  
High Fat ◽  
Middle Aged

In both type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and progressive dysfunction ofβ-cell, leading to the impaired insulin secretion. Here, we show that dietary supplementation of baicalein, a flavone isolated from the roots of Chinese herbScutellaria baicalensis, improved glucose tolerance and enhanced glucose-stimulated insulin secretion (GSIS) in high-fat diet (HFD-) induced middle-aged obese mice. Baicalein had no effect on food intake, body weight gain, circulating lipid profile, and insulin sensitivity in obese mice. Using another mouse model of type 2 diabetes generated by high-fat diet (HFD) feeding and low doses of streptozotocin injection, we found that baicalein treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in these middle-aged obese diabetic mice, which are associated with the improved isletβ-cell survival and mass. In thein vitrostudies, baicalein significantly augmented GSIS and promoted viability of insulin-secreting cells and human islets cultured either in the basal medium or under chronic hyperlipidemic condition. These results demonstrate that baicalein may be a naturally occurring antidiabetic agent by directly modulating pancreaticβ-cell function.

scholarly journals Exercise Affects Blood Glucose Levels and Tissue Chromium Distribution in High-Fat Diet-Fed C57BL6 Mice

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1658 ◽  
Author(s):  
Geng-Ruei Chang ◽  
Po-Hsun Hou ◽  
Wen-Kai Chen ◽  
Chien-Teng Lin ◽  
Hsiao-Pei Tsai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Cell Function ◽  
Body Weight Gain ◽  
Liver Fat ◽  
Standard Diet ◽  
Model Assessment ◽  
Obese Mice ◽  
High Fat

Obesity is commonly associated with hyperglycemia and type 2 diabetes and negatively affects chromium accumulation in tissues. Exercise prevents and controls obesity and type 2 diabetes. However, little information is available regarding chromium changes for regulating glucose homeostasis in high-fat diet (HFD)-fed animals/humans who exercise. Therefore, this study explored the effects of exercise and whether it alters chromium distribution in obese mice. Male C57BL6/J mice aged 4 weeks were randomly divided into two groups and fed either an HFD or standard diet (SD). Each group was subgrouped into two additional groups in which one subgroup was exposed to treadmill exercise for 12 weeks and the other comprised control mice. HFD-fed mice that exercised exhibited significant lower body weight gain, food/energy intake, daily food efficiency, and serum leptin and insulin levels than did HFD-fed control mice. Moreover, exercise reduced fasting glucose and enhanced insulin sensitivity and pancreatic β-cell function, as determined by homeostasis model assessment (HOMA)-insulin resistance and HOMA-β indices, respectively. Exercise also resulted in markedly higher chromium levels within the muscle, liver, fat tissues, and kidney but lower chromium levels in the bone and bloodstream in obese mice than in control mice. However, these changes were not noteworthy in SD-fed mice that exercised. Thus, exercise prevents and controls HFD-induced obesity and may modulate chromium distribution in insulin target tissues.

Ketosis-Prone Type 2 Diabetes: Effect of Hyperglycemia on β-Cell Function and Skeletal Muscle Insulin Signaling

2007 ◽  
Vol 13 (3) ◽  
pp. 283-290 ◽  
Author(s):  
Guillermo Umpierrez ◽  
Dawn Smiley ◽  
Aidar Gosmanov ◽  
Donald Thomason
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Signaling ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function

GLP-1 preserves β cell function via improvement on islet insulin signaling in high fat diet feeding mice

Neuropeptides ◽  
2021 ◽  
Vol 85 ◽  
pp. 102110
Author(s):  
Heng Yang ◽  
Shuo Wang ◽  
Yingchun Ye ◽  
Min Xie ◽  
Yubin Li ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
High Fat Diet ◽  
Cell Function ◽  
High Fat ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Polyphenol-Rich Fraction of Brown AlgaEcklonia cavaCollected from Gijang, Korea, Reduces Obesity and Glucose Levels in High-Fat Diet-Induced Obese Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Eun Young Park ◽  
Eung Hwi Kim ◽  
Mi Hwi Kim ◽  
Young Wan Seo ◽  
Jung Im Lee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Glucose Tolerance ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Glucose Levels

Ecklonia cava (E. cava)is a brown alga that has beneficial effects in models of type 1 and type 2 diabetes. However, the effects ofE. cavaextracts on diet-induced obesity and type 2 diabetes have not been specifically examined. We investigated the effects ofE. cavaon body weight, fat content, and hyperglycemia in high-fat diet- (HFD) induced obese mice and sought the mechanisms involved. C57BL/6 male mice were fed a HFD (60% fat) diet or normal chow. After 3 weeks, the HFD diet group was given extracts (200 mg/kg) ofE. cavaharvested from Jeju (CA) or Gijang (G-CA), Korea or PBS by oral intubation for 8 weeks. Body weights were measured weekly. Blood glucose and glucose tolerance were measured at 7 weeks, and fat pad content and mRNA expression of adipogenic genes and inflammatory cytokines were measured after 8 weeks of treatment. G-CA was effective in reducing body weight gain, body fat, and hyperglycemia and improving glucose tolerance as compared with PBS-HFD mice. The mRNA expression of adipogenic genes was increased, and mRNA expression of inflammatory cytokines and macrophage marker gene was decreased in G-CA-treated obese mice. We suggest that G-CA reduces obesity and glucose levels by anti-inflammatory actions and improvement of lipid metabolism.

scholarly journals High-fat diet-induced glucose dysregulation is independent of changes in islet ACE2 in mice

2016 ◽  
Vol 311 (6) ◽  
pp. R1223-R1233 ◽  
Author(s):  
Harshita Chodavarapu ◽  
Kavaljit H. Chhabra ◽  
Huijing Xia ◽  
Vinayak Shenoy ◽  
Xinping Yue ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Cell Function ◽  
Physiological Role ◽  
Experimental Models ◽  
Minor Role ◽  
Ang Ii ◽  
High Fat

While restoration of ACE2 activity in the pancreas leads to improvement of glycemia in experimental models of Type 2 diabetes, global deficiency in ACE2 disrupts β-cell function and impairs glucose tolerance in mice, demonstrating the physiological role of ACE2 in glucose homeostasis. Although the contribution of pancreatic ACE2 to glucose regulation has been demonstrated in genetic models of diabetes and in models with overexpression of the renin-angiotensin system (RAS), it is unclear whether islet ACE2 is involved in glycemic control in common models of human Type 2 diabetes. To determine whether diet-induced diabetes deregulates glucose homeostasis via reduction of ACE2 in the pancreatic islets, wild-type (WT) and ACE2 knockout (KO) male mice were fed a high-fat diet (HFD) for 16 wk. ACE2 KO mice were more susceptible than WT mice to HFD-mediated glycemic dysregulation. Islet ACE2 activity and expression of various genes, including ANG II type 1a receptor (mAT1aR) were then assessed. Surprisingly, we observed no change in islet ACE2 activity and expression despite local RAS overactivity, indicated by an upregulation of mAT1aR expression. Despite a predominant expression in islet α-cells, further investigation highlighted a minor role for ACE2 on glucagon expression. Further, pancreatic ACE2 gene therapy improved glycemia in HFD-fed WT mice, leading to enhanced glucose-stimulated insulin secretion, reduced pancreatic ANG II levels, fibrosis, and ADAM17 activity. Altogether, our study demonstrates that HFD feeding increases RAS activity and mediates glycemic dysregulation likely through loss of ACE2 present outside the islets but independently of changes in islet ACE2.

scholarly journals Paternal exercise protects mouse offspring from high-fat-diet-induced type 2 diabetes risk by increasing skeletal muscle insulin signaling

2018 ◽  
Vol 57 ◽  
pp. 35-44 ◽  
Author(s):  
Danielle Krout ◽  
James N. Roemmich ◽  
Amy Bundy ◽  
Rolando A. Garcia ◽  
Lin Yan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Diabetes Risk ◽  
High Fat

scholarly journals Liraglutide in Combination with Metformin or Sulfonylurea for the Treatment of Type 2 Diabetes in Adult patients

2012 ◽  
Vol 4 ◽  
pp. CMT.S7283
Author(s):  
Maneesh V Udiawar ◽  
Stephen C Bain
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trials ◽  
Cell Function ◽  
Β Cell ◽  
Beneficial Effects ◽  
Number Of Patients ◽  
Β Cell Function ◽  
Glucagon Like Peptide 1 ◽  
Glycemic Targets

Type 2 diabetes is a progressive disease characterized by decline in β-cell function and insulin resistance. The development of liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, has been shown in clinical trials to be an effective drug with beneficial effects on β-cell function and improved glycemic control, without the side effects of weight gain and hypoglycemia that frequently limit the use of oral anti-diabetic drugs. Furthermore, its prolonged half-life makes it suitable for once daily administration. Liraglutide is demonstrated to be an effective agent in combination with commonly used oral antidiabetic drugs such as metformin and sulphonylureas, with a significant number of patients achieving their glycemic targets without hypoglycemia. In this review, the results from clinical trials utilizing liraglutide in combination with metformin or sulphonylurea are summarized with regards to efficacy and safety.

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