SH2B1 in β-cells regulates glucose metabolism by promoting β-cells survival and islet expansion

Zheng Chen, David L. Morris, Lin Jiang, Yong Liu, Liangyou Rui

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

IGF-1 and insulin promote β-Cells expansion by inhibiting β-Cells death and stimulating β-Cells proliferation, and the phosphatidylinositol (PI) 3-kinase/Akt pathway mediates insulin and IGF-1 action. Impaired β-Cells expansion is a risk factor for type 2 diabetes. Here, we identified SH2B1, which is highly expressed in β-Cellss, as a novel regulator of β-Cells expansion. Silencing of SH2B1 in INS-1 832/13 β-Cellss attenuated insulin- and IGF-1-stimulated activation of the PI 3-kinase/Akt pathway and increased streptozotocin (STZ)-induced apoptosis; conversely, overexpression of SH2B1 had the opposite effects. Activation of the PI 3-kinase/Akt pathway in β-Cellss was impaired in pancreas-specific SH2B1 knockout (PKO) mice fed a high-fat diet (HFD). HFDfed PKO mice also had increased β-Cells apoptosis, decreased β-Cells proliferation, decreased β-Cells mass, decreased pancreatic insulin content, impaired insulin secretion, and exacerbated glucose intolerance. Furthermore, PKO mice were more susceptible to STZ-induced β-Cells destruction, insulin deficiency, and hyperglycemia. These data indicate that SH2B1 in β-Cellss is an important prosurvival and proproliferative protein and promotes compensatory β-Cells expansion in the insulin-resistant state and in response to β-Cells stress.

Original languageEnglish (US)
Pages (from-to)585-595
Number of pages11
JournalDiabetes
Volume63
Issue number2
DOIs
StatePublished - Feb 1 2014

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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