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

16 Citations (Scopus)

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 2014
Externally publishedYes

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Cell Survival
Glucose
Insulin
Phosphatidylinositol 3-Kinase
Insulin-Like Growth Factor I
Knockout Mice
Pancreas
Streptozocin
Cell Proliferation
Apoptosis
Glucose Intolerance
High Fat Diet
Hyperglycemia
Type 2 Diabetes Mellitus
Cell Death
Proteins

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

SH2B1 in β-cells regulates glucose metabolism by promoting β-cells survival and islet expansion. / Chen, Zheng; Morris, David L.; Jiang, Lin; Liu, Yong; Rui, Liangyou.

In: Diabetes, Vol. 63, No. 2, 02.2014, p. 585-595.

Research output: Contribution to journalArticle

Chen, Zheng ; Morris, David L. ; Jiang, Lin ; Liu, Yong ; Rui, Liangyou. / SH2B1 in β-cells regulates glucose metabolism by promoting β-cells survival and islet expansion. In: Diabetes. 2014 ; Vol. 63, No. 2. pp. 585-595.
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