scholarly journals Chronic inflammation exacerbates glucose metabolism disorders in C57BL/6J mice fed with high-fat diet

2013 ◽  
Vol 219 (3) ◽  
pp. 195-204 ◽  
Author(s):  
Yu Wu ◽  
Tingting Wu ◽  
Jun Wu ◽  
Lei Zhao ◽  
Qing Li ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Chronic Inflammation ◽  
High Fat Diet ◽  
Cell Function ◽  
Glucose Metabolism Disorders ◽  
High Fat ◽  
Β Cell ◽  
Islet Mass ◽  
Β Cell Function

Inflammatory stress is closely related to metabolic disease and insulin resistance. The precise cellular mechanism linking obesity and diabetes is largely unknown, but about 14–20% of obese individuals develop diabetes. In this study, we investigated whether chronic inflammation exacerbated glucose metabolism disorder by impairing β cell function in high-fat diet (HFD)-fed C57BL/6J mice. We used s.c. casein injection to induce chronic inflammation in HFD-fed C57BL/6J mice; 14 weeks on a HFD resulted in weight gain, hyperlipidemia, and low insulin sensitivity in these mice which nevertheless had normal blood glucose and serum inflammatory cytokines levels. Casein injection in the background of HFD elevated serum tumor necrosis factor α (TNFα) and serum amyloid A levels and increased TNFα and MCP1 expression in the adipose tissue, liver, and muscle of HFD-fed mice. Chronic inflammation induced by casein injection further decreased insulin sensitivity and insulin signaling, resulting in insulin deficiency and hyperglycemia in these mice. Islet mass and insulin content were markedly increased in HFD mice. However, in contrast with HFD-fed alone, chronic inflammation in HFD-fed mice decreased both islet mass and insulin content, reduced the genetic expression of insulin synthesis and secretion, and increased β cell apoptosis. We conclude that chronic inflammation exacerbated glucose metabolism disorders by impairing β cell function in HFD-fed C57BL/6J mice, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to hyperglycemia.

scholarly journals Maternal high-fat diet impairs glucose metabolism, β-cell function and proliferation in the second generation of offspring rats

2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Yan-Hong Huang ◽  
Ting-Ting Ye ◽  
Chong-Xiao Liu ◽  
Lei Wang ◽  
Yuan-Wen Chen ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
High Fat Diet ◽  
Second Generation ◽  
Cell Function ◽  
High Fat ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

2016 ◽  
Vol 40 (5) ◽  
pp. 1175-1185 ◽  
Author(s):  
Xiuyuan Zhang ◽  
Shan Gao ◽  
Jinfeng Niu ◽  
Pan Li ◽  
Juan Deng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Receptor Agonist ◽  
Cell Function ◽  
Cb2 Receptor ◽  
High Fat ◽  
Β Cell ◽  
Β Cell Function

Background/Aims: The endocannabinoid signalling (ECS) system has been known to regulate glucose homeostasis. Previous studies have suggested that the cannabinoid 2 (CB2) receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance. Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD)/streptozotocin (STZ)-induced mice. Methods: Diabetes was induced in male ICR mice by HFD/STZ and exposed to a CB2 receptor agonist, SER601, for 2- or 4-weeks via subcutaneous implantation of osmotic minipumps. Glucose and insulin tolerance tests were performed at the end of treatment. Islets were isolated for assessment of β-cell function. Pancreases and skeletal muscles were also obtained for histological analyses. Results: Despite a lack of impact on glucose tolerance, substantial improvement on insulin sensitivity was observed in SER601-treated mice, which could partly be attributed to improved islet β-cell function, shown as increased glucose-induced insulin secretion and insulin content. No changes on islet macrophage infiltration or skeletal muscle fat deposition were detectable from SER601-treated mice. However, a major decrease in body weight was recorded at the end of 4-week SER601 exposure, accompanied by a lack of epididymal adipose mass in SER601-treated mice. Conclusion: Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity. Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.

scholarly journals MafB Is Important for Pancreatic β-Cell Maintenance under a MafA-Deficient Condition

2019 ◽  
Vol 39 (17) ◽  
Author(s):  
Gulibaikelamu Xiafukaiti ◽  
Shayida Maimaiti ◽  
Kiyohito Ogata ◽  
Akihiro Kuno ◽  
Takashi Kudo ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Cell Function ◽  
Expression Patterns ◽  
High Fat ◽  
Β Cells ◽  
Β Cell ◽  
Double Knockout ◽  
Adult Mice ◽  
Pathological Conditions ◽  
Β Cell Function

ABSTRACT The pancreatic-islet-enriched transcription factors MafA and MafB have unique expression patterns in β cells in rodents. MafA is specifically expressed in β cells and is a key regulatory factor for maintaining adult β-cell function, whereas MafB plays an essential role in β-cell development during embryogenesis, and its expression in β cells gradually decreases and is restricted to α cells after birth in rodents. However, it was previously observed that MafB started to be reexpressed in insulin-positive (insulin+) β cells in MafA-deficient adult mice. To elucidate how MafB functions in the adult β cell under MafA-deficient conditions, we generated MafA and MafB double-knockout (A0B0) mice in which MafB was specifically deleted from β cells. As a result, the A0B0 mice became more vulnerable to diabetes under a high-fat diet (HFD) treatment, with impaired islet formation and a decreased number of insulin+ β cells because of increased β-cell apoptosis, indicating MafB can take part in the maintenance of adult β cells under certain pathological conditions.

scholarly journals Herring Milt and Herring Milt Protein Hydrolysate Are Equally Effective in Improving Insulin Sensitivity and Pancreatic Beta-Cell Function in Diet-Induced Obese- and Insulin-Resistant Mice

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 635
Author(s):  
Yanwen Wang ◽  
Sandhya Nair ◽  
Jacques Gagnon
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Cell Function ◽  
Protein Hydrolysate ◽  
High Fat ◽  
Β Cell ◽  
Insulin Resistant ◽  
Β Cell Function ◽  
Casein Protein ◽  
Dietary Casein

Although genetic predisposition influences the onset and progression of insulin resistance and diabetes, dietary nutrients are critical. In general, protein is beneficial relative to carbohydrate and fat but dependent on protein source. Our recent study demonstrated that 70% replacement of dietary casein protein with the equivalent quantity of protein derived from herring milt protein hydrolysate (HMPH; herring milt with proteins being enzymatically hydrolyzed) significantly improved insulin resistance and glucose homeostasis in high-fat diet-induced obese mice. As production of protein hydrolysate increases the cost of the product, it is important to determine whether a simply dried and ground herring milt product possesses similar benefits. Therefore, the current study was conducted to investigate the effect of herring milt dry powder (HMDP) on glucose control and the associated metabolic phenotypes and further to compare its efficacy with HMPH. Male C57BL/6J mice on a high-fat diet for 7 weeks were randomized based on body weight and blood glucose into three groups. One group continued on the high-fat diet and was used as the insulin-resistant/diabetic control and the other two groups were given the high-fat diet modified to have 70% of casein protein being replaced with the same amount of protein from HMDP or HMPH. A group of mice on a low-fat diet all the time was used as the normal control. The results demonstrated that mice on the high-fat diet increased weight gain and showed higher blood concentrations of glucose, insulin, and leptin, as well as impaired glucose tolerance and pancreatic β-cell function relative to those on the normal control diet. In comparison with the high-fat diet, the replacement of 70% dietary casein protein with the same amount of HMDP or HMPH protein decreased weight gain and significantly improved the aforementioned biomarkers, insulin sensitivity or resistance, and β-cell function. The HMDP and HMPH showed similar effects on every parameter except blood lipids where HMDP decreased total cholesterol and non-HDL-cholesterol levels while the effect of HMPH was not significant. The results demonstrate that substituting 70% of dietary casein protein with the equivalent amount of HMDP or HMPH protein protects against obesity and diabetes, and HMDP is also beneficial to cholesterol homeostasis.

scholarly journals The Clock GeneRev-erbα Regulates Pancreatic β-Cell Function: Modulation by Leptin and High-Fat Diet

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 592-601 ◽  
Author(s):  
Elaine Vieira ◽  
Laura Marroquí ◽  
Thiago M. Batista ◽  
Ernesto Caballero-Garrido ◽  
Everardo M. Carneiro ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
High Fat ◽  
Β Cell ◽  
Β Cell Function

Dynamics of insulin sensitivity, β-cell function, and β-cell mass during the development of diabetes in fa/fa rats

2007 ◽  
Vol 293 (6) ◽  
pp. E1730-E1735 ◽  
Author(s):  
Brian G. Topp ◽  
Laura L. Atkinson ◽  
Diane T. Finegood
Keyword(s):  
Insulin Sensitivity ◽  
Cell Function ◽  
Cell Mass ◽  
Primary Role ◽  
High Fat ◽  
Β Cell ◽  
Glucose Levels ◽  
Β Cell Function ◽  
Zdf Rats ◽  
Secretory Capacity

Both male Zucker Fatty (mZF) and lower-fat-fed female Zucker diabetic fatty (LF-fZDF) rats are obese but remain normoglycemic. Male ZDF (mZDF) and high-fat-fed female ZDF rats (HF-fZDF) are also obese but develop diabetes between 7 and 10 wk of age. Although these models have been well studied, the mechanisms governing the adaptations to obesity in the normoglycemic animals, and the failure of adaptation in the animals that develop diabetes, remain unclear. Here we use quantitative morphometry and our recently developed coupled β-cell mass (βm), insulin, and glucose model to elucidate the dynamics of insulin sensitivity (SI), β-cell secretory capacity (βsc), and βm in these four animal models. Both groups that remained normoglycemic with increasing obesity (mZF, LF-fZDF) exhibited increased βm and constant βsc in response to a falling SI. In rats that developed hyperglycemia (mZDF, HF-fZDF), there was a greater reduction in SI and slower expansion of βm, with constant βsc. βsc decreased after glucose levels rose above 20 mM. Taken together, these data suggest that excessive insulin resistance and insufficient β m adaptation play a primary role in the pathogenesis of diabetes.

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 TRPM7 is a critical regulator of pancreatic endocrine development and high-fat diet-induced β-cell proliferation

Development ◽  
2021 ◽  
Author(s):  
Molly K. Altman ◽  
Charles M. Schaub ◽  
Matthew T. Dickerson ◽  
Karolina E. Zaborska ◽  
Prasanna K. Dadi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Transient Receptor Potential ◽  
Cell Function ◽  
Cell Mass ◽  
Transient Receptor Potential Channels ◽  
High Fat ◽  
Β Cell ◽  
Β Cell Function

The melastatin subfamily of the transient receptor potential channels (TRPM) are regulators of pancreatic β-cell function. TRPM7 is the most abundant islet TRPM channel; however, the role of TRPM7 in β-cell function has not been determined. Here, we utilized various spatiotemporal transgenic mouse models to investigate how TRPM7 knockout influences pancreatic endocrine development, proliferation, and function. Ablation of TRPM7 within pancreatic progenitors reduced pancreatic size, α-cell and β-cell mass. This resulted in modestly impaired glucose tolerance. However, TRPM7 ablation following endocrine specification or in adult mice did not impact endocrine expansion or glucose tolerance. As TRPM7 regulates cell proliferation, we assessed how TRPM7 influences β-cell hyperplasia under insulin resistant conditions. β-cell proliferation induced by high-fat diet was significantly decreased in TRPM7-deficient β-cells. The endocrine roles of TRPM7 may be influenced by cation flux through the channel, and indeed we find that TRPM7 ablation alters β-cell Mg2+ and reduces the magnitude of elevation in β-cell Mg2+ during proliferation. Together, these findings reveal that TRPM7 controls pancreatic development and β-cell proliferation, which is likely due to regulation of Mg2+ homeostasis.

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