scholarly journals Genistein ameliorates hyperglycemia in a mouse model of nongenetic type 2 diabetes

2012 ◽  
Vol 37 (3) ◽  
pp. 480-488 ◽  
Author(s):  
Zhuo Fu ◽  
Elizabeth R. Gilbert ◽  
Liliane Pfeiffer ◽  
Yanling Zhang ◽  
Yu Fu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glycemic Control ◽  
Mouse Model ◽  
Dietary Intake ◽  
Cell Mass ◽  
Diabetic Mice ◽  
Β Cell ◽  
And Function

While peripheral insulin resistance is common during obesity and aging in mice and people, the progression to type 2 diabetes (T2D) is largely due to loss of β-cell mass and function through apoptosis. We recently reported that genistein, a soy derived isoflavone, can improve glycemic control and β-cell function in insulin-deficient diabetic mice. However, whether it can prevent β-cell loss and diabetes in T2D mice is unknown. Our current study aimed to investigate the effect of dietary supplemented genistein in a nongenetic T2D mouse model. Nongenetic, middle-aged obese diabetic mice were generated by high fat diet and a low dose of streptozotocin injection. The effect of dietary supplementation of genistein on glycemic control and β-cell mass and function was determined. Dietary intake of genistein (250 mg·kg–1 diet) improved hyperglycemia, glucose tolerance, and blood insulin level in obese diabetic mice, whereas it did not affect body weight gain, food intake, fat deposit, plasma lipid profile, and peripheral insulin sensitivity. Genistein increased the number of insulin-positive β-cell in islets, promoted islet β-cell survival, and preserved islet mass. In conclusion, dietary intake of genistein could prevent T2D via a direct protective action on β-cells without alteration of periphery insulin sensitivity.

scholarly journals Development of a Nongenetic Mouse Model of Type 2 Diabetes

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Elizabeth R. Gilbert ◽  
Zhuo Fu ◽  
Dongmin Liu
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mouse Model ◽  
Serum Insulin ◽  
Cell Mass ◽  
Low Fat ◽  
Β Cell ◽  
Islet Mass ◽  
Metabolic Characteristics

Insulin resistance and loss of β-cell mass cause Type 2 diabetes (T2D). The objective of this study was to generate a nongenetic mouse model of T2D. Ninety-six 6-month-old C57BL/6N males were assigned to 1 of 12 groups including (1) low-fat diet (LFD; low-fat control; LFC), (2) LFD with 1 i.p. 40 mg/kg BW streptozotocin (STZ) injection, (3), (4), (5), (6) LFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively, (7) high-fat diet (HFD), (8) HFD with 1 STZ injection, (9), (10), (11), (12) HFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively. After 4 weeks, serum insulin levels were reduced in HFD mice administered at least 2 STZ injections as compared with HFC. Glucose tolerance was impaired in mice that consumed HFD and received 2, 3, or 4 injections of STZ. Insulin sensitivity in HFD mice was lower than that of LFD mice, regardless of STZ treatment. Islet mass was not affected by diet but was reduced by 50% in mice that received 3 STZ injections. The combination of HFD and three 40 mg/kg STZ injections induced a model with metabolic characteristics of T2D, including peripheral insulin resistance and reduced β-cell mass.

scholarly journals Small molecule SWELL1-LRRC8 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes

2021 ◽  
Author(s):  
Susheel K. Gunasekar ◽  
Litao Xie ◽  
Pratik R. Chheda ◽  
Chen Kang ◽  
David M. Kern ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Liver Disease ◽  
Insulin Sensitivity ◽  
Glycemic Control ◽  
Small Molecule ◽  
Fatty Liver Disease ◽  
Β Cell ◽  
Nonalcoholic Fatty Liver

AbstractType 2 diabetes (T2D) is associated with insulin resistance, impaired insulin secretion from the pancreatic β-cell, and nonalcoholic fatty liver disease (NAFLD). SWELL1 (LRRC8a) ablation impairs adipose and skeletal muscle insulin-pAKT2 signaling, β-cell insulin secretion and glycemic control - suggesting that SWELL1-LRRC8 complex dysfunction contributes to T2D pathogenesis. Here, we show that ICl,SWELL and SWELL1 protein are reduced in adipose and β-cells in murine and human T2D. Combining cryo-electron microscopy, molecular docking, medicinal chemistry, and functional studies, we define a structure activity relationship to rationally-designed active derivatives (SN-40X) of a SWELL1 channel inhibitor (DCPIB/SN-401), that bind the SWELL1-LRRC8 hexameric complex, restore SWELL1-LRRC8 protein, plasma membrane trafficking, signaling and islet insulin secretion via SWELL1-dependent mechanisms. In vivo, SN-401 and active SN-40X compounds restore glycemic control and prevents NAFLD by improving insulin-sensitivity and insulin secretion in murine T2D. These findings demonstrate that small molecule SWELL1 modulators restore SWELL1-dependent insulin-sensitivity and insulin secretion in T2D and may represent a first-in-class therapeutic approach for T2D and NAFLD.

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.

Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes

2009 ◽  
Vol 623 (1-3) ◽  
pp. 148-154 ◽  
Author(s):  
James Mu ◽  
Aleksandr Petrov ◽  
George J. Eiermann ◽  
John Woods ◽  
Yun-Ping Zhou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Islet Cell ◽  
Cell Mass ◽  
Rodent Model ◽  
And Function

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.

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.

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