scholarly journals Deficiency of Urokinase Plasminogen Activator May Impair β Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4208 ◽  
Author(s):  
Wu ◽  
Ou ◽  
Chang ◽  
Lin ◽  
Pei ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Insulin Secretion ◽  
Cell Models ◽  
Wild Type ◽  
Β Cell ◽  
Insulin Secretion Rate ◽  
The Relationship

: Background: The relationship between urokinase-type plasminogen activator (uPA) and the development of type 2 diabetes mellitus (T2DM) was investigated in the study by using mice and cell models, as well as patients with T2DM. Methods: In mice models, wild-type and uPA knockout (uPA-/-) BALB/c mice were used for induction of T2DM. In cell models, insulin secretion rate and β cell proliferation were assessed in normal and high glucose after treating uPA siRNA, uPA, or anti-uPA antibody. In our clinical study, patients with T2DM received an oral glucose-tolerance test, and the relationship between uPA and insulin secretion was assessed. Results: Insulin particles and insulin secretion were mildly restored one month after induction in wild-type mice, but not in uPA-/- mice. In cell models, insulin secretion rate and cell proliferation declined in high glucose after uPA silencing either by siRNA or by anti-uPA antibody. After treatment with uPA, β cell proliferation increased in normal glucose. In clinical study, patients with T2DM and higher uPA levels had better ability of insulin secretion than those with lower uPA levels. Conclusion: uPA may play a substantial role in insulin secretion, β cell regeneration, and progressive development of T2DM. Supplementation of uPA might be a novel approach for prevention and treatment of T2DM in the future.

Elevated Circulating LINC-P21 Serves as a Diagnostic Biomarker of Type 2 Diabetes Mellitus and Regulates Pancreatic β-cell Function by Sponging miR-766-3p to Upregulate NR3C2

2020 ◽  
Author(s):  
Zhibin Cao ◽  
Fuwang Yao ◽  
Yuqin Lang ◽  
Xueqiang Feng
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucose Stimulated Insulin Secretion

Abstract Objective The purpose of this study was to evaluate the clinical value and biological function of long non-coding RNA (lncRNA) LINC-P21 in type 2 diabetes mellitus (T2DM), and explore the underlying mechanisms. Methods The expression of LINC-P21 was estimated using quantitative real-time PCR. The functional role of LINC-P21 was explored by gain- and loss-of-function experiments. INS-1 cell proliferation was analyzed using a cell counting kit-8 (CCK-8)assay, and the glucose-stimulated insulin secretion was measured using an ELISA kit. The miRNAs that might be sponged by LINC-P21 were analyzed, and the subsequent target genes were predicted and assessed in INS-1 cells. Results Serum expression of LINC-P21 was elevated in T2DM patients, which was correlated with fasting blood glucose levels and disease diagnosis. The glucose-stimulated insulin secretion and the proliferation of INS-1 cells were enhanced by LINC-P21 knockdown, but the overexpression of LINC-P21 led to opposite effects. miR-766-3p could be directly inhibited by LINC-P21 in INS-1 cells and reverse the effects of LINC-P21 on β-cell function. Additionally, NR3C2 was determined as a target of miR-766-3p, which could be positively regulated by LINC-P21 and had same effects with LINC-P21 on INS-1 cell proliferation and insulin secretion. Conclusion All the data demonstrated that serum elevated LINC-P21 and decreased miR-766-3p serve as candidate diagnostic biomarkers in T2DM patients. LINC-P21 acts as a potential regulator in insulin secretion and proliferation of pancreatic β-cells through targeting miR-766-3p to upregulate NR3C2.

scholarly journals Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus

2020 ◽  
Vol 21 (5) ◽  
pp. 1770
Author(s):  
Nadia Rachdaoui
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Cell Mass ◽  
Β Cells ◽  
Β Cell ◽  
Peripheral Insulin Resistance

Insulin, a hormone produced by pancreatic β-cells, has a primary function of maintaining glucose homeostasis. Deficiencies in β-cell insulin secretion result in the development of type 1 and type 2 diabetes, metabolic disorders characterized by high levels of blood glucose. Type 2 diabetes mellitus (T2DM) is characterized by the presence of peripheral insulin resistance in tissues such as skeletal muscle, adipose tissue and liver and develops when β-cells fail to compensate for the peripheral insulin resistance. Insulin resistance triggers a rise in insulin demand and leads to β-cell compensation by increasing both β-cell mass and insulin secretion and leads to the development of hyperinsulinemia. In a vicious cycle, hyperinsulinemia exacerbates the metabolic dysregulations that lead to β-cell failure and the development of T2DM. Insulin and IGF-1 signaling pathways play critical roles in maintaining the differentiated phenotype of β-cells. The autocrine actions of secreted insulin on β-cells is still controversial; work by us and others has shown positive and negative actions by insulin on β-cells. We discuss findings that support the concept of an autocrine action of secreted insulin on β-cells. The hypothesis of whether, during the development of T2DM, secreted insulin initially acts as a friend and contributes to β-cell compensation and then, at a later stage, becomes a foe and contributes to β-cell decompensation will be discussed.

scholarly journals Differential gene expression between Zucker Fatty rats and Zucker Diabetic Fatty rats: a potential role for the immediate-early gene Egr-1 in regulation of beta cell proliferation

2005 ◽  
Vol 35 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Kay E Garnett ◽  
Philip Chapman ◽  
Julie A Chambers ◽  
Ian D Waddell ◽  
David S W Boam
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Insulin Secretion ◽  
Early Gene ◽  
Β Cell ◽  
Zucker Diabetic Fatty Rats ◽  
Glucose Stimulated Insulin Secretion

The β-cell failure that characterises type 2 diabetes is likely to involve altered expression of many genes. We aimed to identify global changes in gene expression underlying β-cell dysfunction in pre-diabetic Zucker Diabetic Fatty rat islets, followed by functional studies to verify our findings. Gene expression profiles in islets from 6-week-old Zucker Diabetic Fatty rats and Zucker Fatty rat controls were analysed using Affymetrix microarrays. Totally 977 genes were found to be differentially regulated, comprising large groups of membrane and structural proteins, kinases, channels, receptors, transporters, growth factors and transcription factors. We are particularly interested in transcription factors, which can have profound effects on cellular function. Thus a subset of those with no role yet defined in the β-cell was selected for further study namely the immediate-early gene Egr-1, PAG608, rCGR19 and mSin3b. Tissue specificity of these factors varied but interestingly Egr-1 expression was highly enriched in the pancreatic islet. To determine a possible role of Egr-1 in the β-cell, Egr-1 expression in INS-1 cells was silenced using RNA interference (RNAi). Glucose-stimulated insulin secretion in these cells was then measured using ELISA and cell proliferation was measured by [3H]thymidine incorporation. Small interfering RNA (siRNA)-mediated silencing of the Egr-1 gene inhibited its induction by glucose but had no observable effect on glucose-stimulated insulin secretion. However, Egr-1 gene silencing did inhibit proliferation of INS-1 cells in a glucose-independent manner. Our studies have revealed a role for Egr-1 and suggest that reduced Egr-1 gene expression may contribute to decreased β-cell proliferation and the consequent β-cell failure observed in the later stages of type 2 diabetes.

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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