Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells

Mohan, Ramkumar; Mao, Yiping; Zhang, Shungang; Zhang, Yu-Wei; Xu, Cheng‐Ran; Gradwohl, Gérard; Tang, Xiaoqing

doi:10.1074/jbc.m115.650705

Cited by 46 publications

(39 citation statements)

References 69 publications

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“…Inactivation of miR-375 in mice is associated with reduced ␤-cell mass, increased ␣-cell number and plasma glucagon levels, hyperglycemia, reduced insulin secretion, and disrupted islets architecture (64). miR-483 also shows similar patterns of regulation of insulin and glucagon secretion (53). Downregulated expression of miR-375 in ob/ob mice results in reduced ␤-cell mass and plasma insulin levels and severe diabetes.…”

Section: Regulation Of ␤-Cell Development and Insulin Secretion By MImentioning

confidence: 85%

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Biological roles of microRNAs in the control of insulin secretion and action

Caldérari

Diawara

Garaud

et al. 2017

Physiological Genomics

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microRNAs (miRNAs) are intracellular and circulating molecular components contributing to genome expression control through binding mRNA targets, which generally results in downregulated mRNA expression. One miRNA can target several mRNAs, and one transcript can be targeted by several miRNAs, resulting in complex fine-tuning of regulation of gene networks and signaling pathways. miRNAs regulate metabolism, adipocyte differentiation, pancreatic development, β-cell mass, insulin biosynthesis, secretion, and signaling, and their role in diabetes and obesity is emerging. Their pathophysiological effects are essentially dependent on cellular coexpression with their mRNA targets, which can show tissue-specific transcriptional responses to disease conditions and environmental challenges. Current knowledge of miRNA biology and their impact on the pathogenesis of diabetes and obesity is based on experimental data documenting miRNA expression generally in single tissue types that can be correlated with expression of target mRNAs to integrate miRNA in functional pathways and gene networks. Here we present results from the most significant studies dealing with miRNA function in liver, fat, skeletal muscle, and endocrine pancreas and their implication in diabetes and obesity

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Section: Regulation Of ␤-Cell Development and Insulin Secretion By MImentioning

confidence: 85%

“…On the other hand miR-29b was ubiquitously expressed in all tested tissues. miR-375 and miR-483 are remarkable examples of differential miRNA-mediated intrapancreatic regulation, as they stimulate insulin secretion by ␤-cells and decrease glucagon secretion by ␣-cells (53,64).…”

Section: Conservation and Specificity Of Mirna Expression Across Multmentioning

confidence: 99%

Biological roles of microRNAs in the control of insulin secretion and action

Caldérari

Diawara

Garaud

et al. 2017

Physiological Genomics

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show abstract

“…miRNAs play a crucial role in organ formation during embryogenesis, including pancreas development and β-cell differentiation (14). Moreover, they display an important role in maintaining functional β-cell mass (15–17) and endocrine cell identity (18,19) during adult life.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells

et al. 2016

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Type 1 diabetes (T1D) is an autoimmune disease leading to β-cell destruction. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to β-cell death in T1D and their target genes remain to be clarified. We performed an miRNA expression profile on human islet preparations exposed to the cytokines IL-1β plus IFN-γ. Confirmation of miRNA and target gene modification in human β-cells was performed by real-time quantitative PCR. Single-stranded miRNAs inhibitors were used to block selected endogenous miRNAs. Cell death was measured by Hoechst/propidium iodide staining and activation of caspase-3. Fifty-seven miRNAs were detected as modulated by cytokines. Three of them, namely miR-23a-3p, miR-23b-3p, and miR-149-5p, were downregulated by cytokines and selected for further studies. These miRNAs were found to regulate the expression of the proapoptotic Bcl-2 proteins DP5 and PUMA and consequent human β-cell apoptosis. These results identify a novel cross talk between a key family of miRNAs and proapoptotic Bcl-2 proteins in human pancreatic β-cells, broadening our understanding of cytokine-induced β-cell apoptosis in early T1D.

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“…miRNAs control the expression of many genes and are involved in a variety of crucial biological processes, which include development, differentiation, apoptosis, cell proliferation and diseases . Recently, a number of studies have demonstrated that miRNAs can regulate the development of pancreatic cells .…”

Section: Introductionmentioning

confidence: 99%