Programmed disorders of β-cell development and function as one cause for type 2 diabetes? The GK rat paradigm

2005 ◽  
Vol 21 (6) ◽  
pp. 495-504 ◽  
Author(s):  
Bernard Portha
Keyword(s):  
Type 2 Diabetes ◽  
Cell Development ◽  
Gk Rat ◽  
Β Cell ◽  
And Function

scholarly journals Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians

2011 ◽  
Vol 56 (10) ◽  
pp. 695-700 ◽  
Author(s):  
Sreenivas Chavali ◽  
Anubha Mahajan ◽  
Rubina Tabassum ◽  
Om Prakash Dwivedi ◽  
Ganesh Chauhan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Development ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
North Indians ◽  
And Function

Pioglitazone preserves pancreatic islet structure and insulin secretory function in three murine models of type 2 diabetes

2004 ◽  
Vol 286 (1) ◽  
pp. E116-E122 ◽  
Author(s):  
A. R. Diani ◽  
Geri Sawada ◽  
Beatrice Wyse ◽  
F. T. Murray ◽  
Mehmood Khan
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Insulin ◽  
Glycosylated Hemoglobin ◽  
Β Cells ◽  
Β Cell ◽  
Insulin Dependent ◽  
Plasma Insulin Levels ◽  
And Function ◽  
And Control

Thiazolidinediones may slow the progression of type 2 diabetes by preserving pancreatic β-cells. The effects of pioglitazone (PIO) on structure and function of β-cells in KKA(y), C57BL/6J ob/ob, and C57BL/KsJ db/db mice (genetic models of type 2 diabetes) were examined. ob/ob ( n = 7) and db/db ( n = 9) mice were randomly assigned to 50-125 mg·kg body wt-1·day-1of PIO in chow beginning at 6-10 wk of age. Control ob/ob ( n = 7) and db/db mice ( n = 9) were fed chow without PIO. KKA(y) mice ( n = 15) were fed PIO daily at doses of 62-144 mg·kg body wt-1·day-1. Control KKA(y) mice ( n = 10) received chow without PIO. Treatment continued until euthanasia at 14-26 wk of age. Blood was collected at baseline (before treatment) and just before euthanasia and was analyzed for glucose, glycosylated hemoglobin, and plasma insulin. Some of the splenic pancreas of each animal was resected and partially sectioned for light or electron microscopy. The remainder of the pancreas was assayed for insulin content. Compared with baseline and control groups, PIO treatment significantly reduced blood glucose and glycosylated hemoglobin levels. Plasma insulin levels decreased significantly in ob/ob mice treated with PIO. All groups treated with PIO exhibited significantly greater β-cell granulation, evidence of reduced β-cell stress, and 1.5- to 15-fold higher levels of pancreatic insulin. The data from these studies suggest that comparable effects would be expected to slow the progression of type 2 diabetes, either delaying or possibly preventing progression to an insulin-dependent state.

scholarly journals The long non-coding RNA Pax6os1/PAX6-AS1 modulates pancreatic β-cell identity and function

2020 ◽  
Author(s):  
Livia Lopez-Noriega ◽  
Rebecca Callingham ◽  
Aida Martinez-Sánchez ◽  
Grazia Pizza ◽  
Nejc Haberman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
High Glucose ◽  
High Fat Diet ◽  
High Fat ◽  
Β Cell ◽  
And Function

AbstractLong non-coding RNAs (lncRNAs) are emerging as crucial regulators of β-cell development and function. Consequently, the mis-expression of members of this group may contribute to the risk of type 2 diabetes (T2D). Here, we investigate roles for an antisense lncRNA expressed from the Pax6 locus (annotated as Pax6os1 in mice and PAX6-AS1 in humans) in β-cell function. The transcription factor Pax6 is required for the development of pancreatic islets and maintenance of a fully differentiated β-cell phenotype. Pax6os1/PAX6-AS1 expression was increased in pancreatic islets and β-cell lines at high glucose concentrations, in islets from mice fed a high fat diet, and in those from patients with type 2 diabetes. Silencing or deletion of Pax6os1/PAX6-AS1 in MIN6 cells and EndoC-βH1cells, respectively, upregulated β-cell signature genes, including insulin. Moreover, shRNA-mediated silencing of PAX6-AS1 in human islets not only increased insulin mRNA, but also enhanced glucose-stimulated insulin secretion and calcium dynamics. In contrast, inactivation of Pax6os1 in mice was largely without effect on glucose homeostasis, though female Pax6os1 null mice on high fat diet (HFD) showed a tendency towards enhanced glucose clearance. Together, our results suggest that increased expression of PAX6-AS1 at high glucose levels may contribute to β-cell dedifferentiation and failure in some forms of type 2 diabetes. Thus, targeting PAX6-AS1 may provide a promising strategy to enhance insulin secretion and improve glucose homeostasis in type 2 diabetes.

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.

BACE2 suppression promotes β-cell survival and function in a model of type 2 diabetes induced by human islet amyloid polypeptide overexpression

2017 ◽  
Vol 74 (15) ◽  
pp. 2827-2838 ◽  
Author(s):  
Gema Alcarraz-Vizán ◽  
Carlos Castaño ◽  
Montse Visa ◽  
Joel Montane ◽  
Joan-Marc Servitja ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Survival ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Β Cell ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
And Function

scholarly journals Clinical Potential of Extracellular Vesicles in Type 2 Diabetes

2021 ◽  
Vol 11 ◽  
Author(s):  
Jie Liu ◽  
Xin Sun ◽  
Fu-Liang Zhang ◽  
Hang Jin ◽  
Xiu-Li Yan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Extracellular Vesicles ◽  
Sedentary Lifestyle ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Peripheral Tissues ◽  
And Function ◽  
Clinical Potential

Type 2 diabetes (T2D) is a major public health disease which is increased in incidence and prevalence throughout the whole world. Insulin resistance (IR) in peripheral tissues and insufficient pancreatic β-cell mass and function have been recognized as primary mechanisms in the pathogenesis of T2D, while recently, systemic chronic inflammation resulting from obesity and a sedentary lifestyle has also gained considerable attention in T2D progression. Nowadays, accumulating evidence has revealed extracellular vesicles (EVs) as critical mediators promoting the pathogenesis of T2D. They can also be used in the diagnosis and treatment of T2D and its complications. In this review, we briefly introduce the basic concepts of EVs and their potential roles in the pathogenesis of T2D. Then, we discuss their diagnostic and therapeutic potentials in T2D and its complications, hoping to open new prospects for the management of T2D.

Could lncRNAs contribute to β-cell identity and its loss in Type 2 diabetes?

2013 ◽  
Vol 41 (3) ◽  
pp. 797-801 ◽  
Author(s):  
Timothy J. Pullen ◽  
Guy A. Rutter
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Cell Types ◽  
Human Populations ◽  
Β Cell ◽  
Cell Identity ◽  
Genome Wide ◽  
And Function

The progression of Type 2 diabetes is accompanied by diminishing islet β-cell mass and function. It has been proposed that β-cells are lost not only through apoptosis, but also by dedifferentiating into progenitor-like cells. There is therefore much interest in the mechanisms which define and maintain β-cell identity. The advent of genome-wide analyses of chromatin modifications has highlighted the role of epigenetic factors in determining cell identity. There is also evidence from both human populations and animal models for an epigenetic component in susceptibility to Type 2 diabetes. The mechanisms responsible for defining the epigenetic landscape in individual cell types are poorly understood, but there is growing evidence of a role for lncRNAs (long non-coding RNAs) in this process. In the present paper, we discuss some of the mechanisms through which lncRNAs may contribute to β-cell identity and Type 2 diabetes risk.

scholarly journals Cell-Free DNA Fragments as Biomarkers of Islet β-Cell Death in Obesity and Type 2 Diabetes

2021 ◽  
Vol 22 (4) ◽  
pp. 2151
Author(s):  
Marilyn Arosemena ◽  
Farah A. Meah ◽  
Kieren J. Mather ◽  
Sarah A. Tersey ◽  
Raghavendra G. Mirmira
Keyword(s):  
Type 2 Diabetes ◽  
Cell Death ◽  
Cell Mass ◽  
Dna Fragments ◽  
Β Cell ◽  
Modified Dna ◽  
Function Loss ◽  
And Function ◽  
Study Designs

Type 2 diabetes (T2D) typically occurs in the setting of obesity and insulin resistance, where hyperglycemia is associated with decreased pancreatic β-cell mass and function. Loss of β-cell mass has variably been attributed to β-cell dedifferentiation and/or death. In recent years, it has been proposed that circulating epigenetically modified DNA fragments arising from β cells might be able to report on the potential occurrence of β-cell death in diabetes. Here, we review published literature of DNA-based β-cell death biomarkers that have been evaluated in human cohorts of islet transplantation, type 1 diabetes, and obesity and type 2 diabetes. In addition, we provide new data on the applicability of one of these biomarkers (cell free unmethylated INS DNA) in adult cohorts across a spectrum from obesity to T2D, in which no significant differences were observed, and compare these findings to those previously published in youth cohorts where differences were observed. Our analysis of the literature and our own data suggest that β-cell death may occur in subsets of individuals with obesity and T2D, however a more sensitive method or refined study designs are needed to provide better alignment of sampling with disease progression events.

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