scholarly journals Islet Inflammation Impairs the Pancreatic β-Cell in Type 2 Diabetes

Physiology ◽  
2009 ◽  
Vol 24 (6) ◽  
pp. 325-331 ◽  
Author(s):  
Marc Y. Donath ◽  
Marianne Böni-Schnetzler ◽  
Helga Ellingsgaard ◽  
Jan A. Ehses
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Metabolic Stress ◽  
Innate Immune ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Amyloid Deposits ◽  
Impaired Insulin ◽  
Islet Inflammation

Onset of Type 2 diabetes occurs when the pancreatic β-cell fails to adapt to the increased insulin demand caused by insulin resistance. Morphological and therapeutic intervention studies have uncovered an inflammatory process in islets of patients with Type 2 diabetes characterized by the presence of cytokines, immune cells, β-cell apoptosis, amyloid deposits, and fibrosis. This insulitis is due to a pathological activation of the innate immune system by metabolic stress and governed by IL-1 signaling. We propose that this insulitis contributes to the decrease in β-cell mass and the impaired insulin secretion observed in patients with Type 2 diabetes.

Analysis of compensatory β-cell response in mice with combined mutations of Insr and Irs2

2007 ◽  
Vol 292 (6) ◽  
pp. E1694-E1701 ◽  
Author(s):  
Jane J. Kim ◽  
Yoshiaki Kido ◽  
Philipp E. Scherer ◽  
Morris F. White ◽  
Domenico Accili
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Response ◽  
Cell Mass ◽  
Comprehensive Treatment ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Impaired Insulin

Type 2 diabetes results from impaired insulin action and β-cell dysfunction. There are at least two components to β-cell dysfunction: impaired insulin secretion and decreased β-cell mass. To analyze how these two variables contribute to the progressive deterioration of metabolic control seen in diabetes, we asked whether mice with impaired β-cell growth due to Irs2 ablation would be able to mount a compensatory response in the background of insulin resistance caused by Insr haploinsufficiency. As previously reported, ∼70% of mice with combined Insr and Irs2 mutations developed diabetes as a consequence of markedly decreased β-cell mass. In the initial phases of the disease, we observed a robust increase in circulating insulin levels, even as β-cell mass gradually declined, indicating that replication-defective β-cells compensate for insulin resistance by increasing insulin secretion. These data provide further evidence for a heterogeneous β-cell response to insulin resistance, in which compensation can be temporarily achieved by increasing function when mass is limited. The eventual failure of compensatory insulin secretion suggests that a comprehensive treatment of β-cell dysfunction in type 2 diabetes should positively affect both aspects of β-cell physiology.

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 Early administration of dapagliflozin preserves pancreatic β‐cell mass through a legacy effect in a mouse model of type 2 diabetes

2018 ◽  
Vol 10 (3) ◽  
pp. 577-590 ◽  
Author(s):  
Ayumi Kanno ◽  
Shun‐ichiro Asahara ◽  
Mao Kawamura ◽  
Ayuko Furubayashi ◽  
Shoko Tsuchiya ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Early Administration ◽  
Legacy Effect

scholarly journals Administration of mulberry leaves maintains pancreatic β-cell mass in obese/type 2 diabetes mellitus mouse model

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Patlada Suthamwong ◽  
Manabu Minami ◽  
Toshiaki Okada ◽  
Nonomi Shiwaku ◽  
Mai Uesugi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mouse Model ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Mulberry Leaves

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.

Combination of TS-021 with metformin improves hyperglycemia and synergistically increases pancreatic β-cell mass in a mouse model of type 2 diabetes

Life Sciences ◽  
2011 ◽  
Vol 89 (17-18) ◽  
pp. 662-670 ◽  
Author(s):  
Atsushi Tajima ◽  
Takashi Hirata ◽  
Kazuo Taniguchi ◽  
Yukiko Kondo ◽  
Sota Kato ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell

Pancreatic β-cell mass in European subjects with type 2 diabetes

2008 ◽  
Vol 10 ◽  
pp. 32-42 ◽  
Author(s):  
J. Rahier ◽  
Y. Guiot ◽  
R. M. Goebbels ◽  
C. Sempoux ◽  
J. C. Henquin
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell

scholarly journals Macrophages, cytokines and β-cell death in Type 2 diabetes

2008 ◽  
Vol 36 (3) ◽  
pp. 340-342 ◽  
Author(s):  
Jan A. Ehses ◽  
Marianne Böni-Schnetzler ◽  
Mirjam Faulenbach ◽  
Marc Y. Donath
Keyword(s):  
Type 2 Diabetes ◽  
Immune Cell ◽  
Metabolic Stress ◽  
Interleukin 1Β ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Amyloid Deposits ◽  
Promising Therapeutic Approach ◽  
Islet Inflammation

The pathology of islets from patients with Type 2 diabetes displays an inflammatory process characterized by the presence of immune cell infiltration, cytokines, apoptotic cells, amyloid deposits and, eventually, fibrosis. Indeed, analysis of β-cells from patients with Type 2 diabetes displays increased IL-1β (interleukin 1β) expression. Furthermore, increased islet-associated macrophages are observed in human Type 2 diabetic patients and in most animal models of diabetes. Importantly, increased numbers of macrophages are detectable very early in high-fat-fed mice islets, before the onset of diabetes. These immune cells are probably attracted by islet-derived chemokines, produced in response to metabolic stress, and under the control of IL-1β. It follows that modulation of intra-islet inflammatory mediators, particularly interleukin-1β, may prevent islet inflammation in Type 2 diabetes and therefore presents itself as a promising therapeutic approach.

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