scholarly journals Na+/Ca2+ Exchanger a Druggable Target to Promote β-Cell Proliferation and Function

2018 ◽  
Vol 2 (7) ◽  
pp. 631-645
Author(s):  
Julien Papin ◽  
Francesco Paolo Zummo ◽  
Nathalie Pachera ◽  
Claudiane Guay ◽  
Romano Regazzi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Β Cell ◽  
And Function

Tead1 Reciprocally Regulates Adult β-Cell Proliferation and Function to Maintain Glucose Homeostasis

2020 ◽  
Author(s):  
Jeongkyung Lee ◽  
Ruya Liu ◽  
Byung S. Kim ◽  
Yiqun Zhang ◽  
Feng Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glucose Homeostasis ◽  
Β Cell ◽  
And Function

Reduced Compensatory β-Cell Proliferation in Nfatc3-Deficient Mice Fed on High-Fat Diet

2019 ◽  
Author(s):  
Li Hu ◽  
Fengli He ◽  
Yan Luo ◽  
Hairong Luo ◽  
Luo Hai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
High Fat Diet ◽  
Compensatory Growth ◽  
Pancreatic Β Cell ◽  
High Fat ◽  
Β Cell ◽  
Primary Mouse ◽  
Mouse Islets ◽  
And Function

Abstract Background High-fat-diet induces pancreatic β-cell compensatory proliferation, and impairments in pancreatic β-cell proliferation and function can lead to defects in insulin secretion and diabetes. NFATc3 is important for HFD-induced adipose tissue inflammation. But it is unknown whether NFATc3 is required for β cell compensatory growth in mice fed with HFD. Methods NFATc3 mRNA and protein expression levels were quantified by RT-qPCR and Western blotting, respectively, in pancreatic islets of WT mice fed on HFD for 12–20 weeks. Adenoviral-mediated overexpression of NFATc3 were conducted in Min6 cells and cultured primary mouse islets. NFATc3-/- mice and WT control mice were fed with HFD and metabolic and functional parameters were measured. Results We observed that the NFATc3 expression level was reduced in the islets of high-fat-diet (HFD)-fed mice. Adenovirus-mediated overexpression of NFATc3 enhanced glucose-stimulated insulin secretion and β-cell gene expression in cultured primary mouse islets. Nfatc3-/- mice initially developed similar glucose tolerance at 2–4 weeks after HFD feeding than HFD-fed WT mice, but Nfatc3-/- mice developed improved glucose tolerance and insulin sensitivity after 8 weeks of HFD feeding compared to Nfatc3+/+fed with HFD. Furthermore, Nfatc3-/- mice on HFD exhibited decreased β-cell mass and reduced expression of genes important for β-cell proliferation and function compared to Nfatc3+/+mice on HFD. Conclusions The findings suggested that NFATc3 played a role in maintaining the pancreatic β-cell compensatory growth and gene expression in response to obesity.

Nerve Growth Factor Improves Survival and Function of Transplanted Islets Via TrkA-mediated β Cell Proliferation and Revascularization

2015 ◽  
Vol 99 (6) ◽  
pp. 1132-1143 ◽  
Author(s):  
Tatsuo Hata ◽  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Haruyuki Tsuchiya ◽  
Masahiko Fukase ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Β Cell ◽  
Nerve Growth ◽  
And Function

scholarly journals Pancreatic β-Cell Proliferation in Obesity1,2

2014 ◽  
Vol 5 (3) ◽  
pp. 278-288 ◽  
Author(s):  
Amelia K. Linnemann ◽  
Mieke Baan ◽  
Dawn Belt Davis
Keyword(s):  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Extracellular Signals ◽  
Secreted Factors ◽  
And Function ◽  
Hepatocyte Growth

Abstract Because obesity rates have increased dramatically over the past 3 decades, type 2 diabetes has become increasingly prevalent as well. Type 2 diabetes is associated with decreased pancreatic β-cell mass and function, resulting in inadequate insulin production. Conversely, in nondiabetic obesity, an expansion in β-cell mass occurs to provide sufficient insulin and to prevent hyperglycemia. This expansion is at least in part due to β-cell proliferation. This review focuses on the mechanisms regulating obesity-induced β-cell proliferation in humans and mice. Many factors have potential roles in the regulation of obesity-driven β-cell proliferation, including nutrients, insulin, incretins, hepatocyte growth factor, and recently identified liver-derived secreted factors. Much is still unknown about the regulation of β-cell replication, especially in humans. The extracellular signals that activate proliferative pathways in obesity, the relative importance of each of these pathways, and the extent of cross-talk between these pathways are important areas of future study.

scholarly journals Expansion of Islet-Resident Macrophages Leads to Inflammation Affecting β Cell Proliferation and Function in Obesity

2019 ◽  
Vol 29 (2) ◽  
pp. 457-474.e5 ◽  
Author(s):  
Wei Ying ◽  
Yun Sok Lee ◽  
Yi Dong ◽  
Jason S. Seidman ◽  
Meixiang Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Β Cell ◽  
And Function

scholarly journals Tead1 reciprocally regulates adult β-cell proliferation and function

2020 ◽  
Author(s):  
Jeongkyung Lee ◽  
Ruya Liu ◽  
Byung S. Kim ◽  
Yiqun Zhang ◽  
Feng Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Cell Mass ◽  
Β Cells ◽  
Β Cell ◽  
Critical Function ◽  
Reciprocal Regulation ◽  
Functional Competence ◽  
And Function

SummaryDiabetes ensues when there is a net decrease in functional β-cell mass. Efforts to increase β-cell mass are limited by a concurrent loss of mature function. The molecular mechanisms underlying the reciprocal regulation between β-cell proliferation and mature function are unclear. Here, we demonstrate that constitutive and inducible genetic deletion of Tead1 in mouse β-cells leads to diabetes. Tead1, the transcription factor downstream of the mammalian-hippo pathway, has a developmental stage-specific critical function in β-cells and is required for maintenance of mature β-cell functional competence by direct transcriptional regulation of a network of critical β-cell transcription factors, including, Pdx1, Nkx6.1 and MafA. Concurrently, Tead1 directly activates Cdkn2a transcription in adult β-cells to inhibit proliferation. Studies in human β-cells demonstrate that Tead1 plays a similar regulatory role. Taken together, our findings uncover the non-redundant role of Tead1 in modulating the balance between proliferative capacity and functional competence.

INCRETIN AND DIABETES

2011 ◽  
pp. 5-10
Author(s):  
Huu Dang Tran
Keyword(s):  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Glycaemic Control ◽  
Animal Studies ◽  
Dipeptidyl Peptidase ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Glucose Sensitivity ◽  
Cell Glucose

The incretins are peptide hormones secreted from the gut in response to food. They increase the secretion of insulin. The incretin response is reduced in patients with type 2 diabetes so drugs acting on incretins may improve glycaemic control. Incretins are metabolised by dipeptidyl peptidase, so selectively inhibiting this enzyme increases the concentration of circulating incretins. A similar effect results from giving an incretin analogue that cannot be cleaved by dipeptidyl peptidase. Studies have identified other actions including improvement in pancreatic β cell glucose sensitivity and, in animal studies, promotion of pancreatic β cell proliferation and reduction in β cell apoptosis.

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