scholarly journals Impact of the Dipeptidyl Peptidase-4 Inhibitor Vildagliptin on Glucose Tolerance and β-Cell Function and Mass in Insulin Receptor Substrate-2-Knockout Mice Fed a High-Fat Diet

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1093-1102 ◽  
Author(s):  
Koichiro Sato ◽  
Akinobu Nakamura ◽  
Jun Shirakawa ◽  
Tomonori Muraoka ◽  
Yu Togashi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Cell Function ◽  
Insulin Receptor Substrate ◽  
High Fat ◽  
Β Cell ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Β Cell Function

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.

scholarly journals Inhibition of Small Maf Function in Pancreatic β-Cells Improves Glucose Tolerance Through the Enhancement of Insulin Gene Transcription and Insulin Secretion

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3570-3580 ◽  
Author(s):  
Hiroshi Nomoto ◽  
Takuma Kondo ◽  
Hideaki Miyoshi ◽  
Akinobu Nakamura ◽  
Yoko Hida ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Cell Function ◽  
High Fat ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function

The large-Maf transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) has been found to be crucial for insulin transcription and synthesis and for pancreatic β-cell function and maturation. However, insights about the effects of small Maf factors on β-cells are limited. Our goal was to elucidate the function of small-Maf factors on β-cells using an animal model of endogenous small-Maf dysfunction. Transgenic (Tg) mice with β-cell-specific expression of dominant-negative MafK (DN-MafK) experiments, which can suppress the function of all endogenous small-Mafs, were fed a high-fat diet, and their in vivo phenotypes were evaluated. Phenotypic analysis, glucose tolerance tests, morphologic examination of β-cells, and islet experiments were performed. DN-MafK-expressed MIN6 cells were also used for in vitro analysis. The results showed that DN-MafK expression inhibited endogenous small-Maf binding to insulin promoter while increasing MafA binding. DN-MafK Tg mice under high-fat diet conditions showed improved glucose metabolism compared with control mice via incremental insulin secretion, without causing changes in insulin sensitivity or MafA expression. Moreover, up-regulation of insulin and glucokinase gene expression was observed both in vivo and in vitro under DN-MafK expression. We concluded that endogenous small-Maf factors negatively regulates β-cell function by competing for MafA binding, and thus, the inhibition of small-Maf activity can improve β-cell function.

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

2020 ◽  
Author(s):  
Molly K. Altman ◽  
Charles M. Schaub ◽  
Matthew T. Dickerson ◽  
Prasanna K. Dadi ◽  
Sarah M. Graff ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Cell Function ◽  
Transient Receptor Potential Channels ◽  
High Fat ◽  
Β Cell ◽  
Pancreatic Progenitor ◽  
Insulin Resistant ◽  
Β Cell Function

ABSTRACTThe 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, as well as α-cell and β-cell mass. This resulted in impaired glucose tolerance due to decreased serum insulin levels. However, ablation of TRPM7 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 intracellular Mg2+. Together, these findings reveal that TRPM7 controls pancreatic progenitor expansion and β-cell proliferation, which is likely due to regulation of Mg2+ homeostasis.SummaryThis manuscript identifies a critical developmental role for TRPM7 channels in pancreatic progenitor cells. The manuscript also determines that TRPM7 plays a key role in β-cell proliferation under insulin-resistant conditions.

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

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 β-cell knockout of SENP1 reduces responses to incretins and worsens oral glucose tolerance in high fat diet-fed mice

2021 ◽  
Author(s):  
Haopeng Lin ◽  
Nancy Smith ◽  
Aliya F Spigelman ◽  
Kunimasa Suzuki ◽  
Mourad Ferdaoussi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Glucagon Secretion ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
High Fat ◽  
Β Cell ◽  
Islet Mass

SUMOylation reduces oxidative stress and preserves islet mass at the expense of robust insulin secretion. To investigate a role for the deSUMOylating enzyme <u>sen</u>trin-specific <u>p</u>rotease <u>1</u> (SENP1) following metabolic stress, we put pancreas/gut-specific SENP1 knockout mice (pSENP1-KO) on a high fat diet (HFD). Male pSENP1-KO mice were more glucose intolerant following HFD than littermate controls, but only in response to oral glucose. A similar phenotype was observed in females. Plasma glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide 1 (GLP-1) responses were identical in pSENP1-KO and -WT littermates, including the HFD-induced upregulation of GIP responses. Islet mass was not different, but insulin secretion and β-cell exocytotic responses to the GLP-1 receptor agonist Exendin-4 (Ex4) and GIP were impaired in islets lacking SENP1. Glucagon secretion from pSENP1-KO islets was also reduced, so we generated β-cell-specific SENP1 knockout mice (βSENP1-KO). These phenocopied the pSENP1-KO mice with selective impairment in oral glucose tolerance following HFD, preserved islet mass expansion, and impaired β-cell exocytosis and insulin secretion to Ex4 and GIP without changes in cAMP or Ca<sup>2+</sup> levels. Thus, β-cell SENP1 limits oral glucose intolerance following HFD by ensuring robust insulin secretion at a point downstream of incretin signaling.

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