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RIG-I inhibits pancreatic β cell proliferation through competitive binding of activated Src.

ABSTRACT: Nutrition is a necessary condition for cell proliferation, including pancreatic β cells; however, over-nutrition, and the resulting obesity and glucolipotoxicity, is a risk factor for the development of Type 2 diabetes mellitus (DM), and causes inhibition of pancreatic β-cells proliferation and their loss of compensation for insulin resistance. Here, we showed that Retinoic acid (RA)-inducible gene I (RIG-I) responds to nutrient signals and induces loss of β cell mass through G1 cell cycle arrest. Risk factors for type 2 diabetes (e.g., glucolipotoxicity, TNF-α and LPS) activate Src in pancreatic β cells. Elevated RIG-I modulated the interaction of activated Src and STAT3 by competitive binding to STAT3. Elevated RIG-I downregulated the transcription of SKP2, and increased the stability and abundance of P27 protein in a STAT3-dependent manner, which was associated with inhibition of β cell growth elicited by Src. These results supported a role for RIG-I in β cell mass loss under conditions of metabolic surplus and suggested that RIG-I-induced blocking of Src/STAT3 signalling might be involved in G1 phase cycle arrest through the Skp2/P27 pathway in pancreatic β cells.

SUBMITTER: Pan Y

PROVIDER: S-EPMC4923948 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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RIG-I inhibits pancreatic β cell proliferation through competitive binding of activated Src.

Pan Yi Y Li GuangMing G Zhong HengGao H Chen MeiJuan M Chen TingTing T Gao LiLi L Wu HuiWen H Guo Jun J

Scientific reports 20160628

Nutrition is a necessary condition for cell proliferation, including pancreatic β cells; however, over-nutrition, and the resulting obesity and glucolipotoxicity, is a risk factor for the development of Type 2 diabetes mellitus (DM), and causes inhibition of pancreatic β-cells proliferation and their loss of compensation for insulin resistance. Here, we showed that Retinoic acid (RA)-inducible gene I (RIG-I) responds to nutrient signals and induces loss of β cell mass through G1 cell cycle arres ...[more]

PMID: 27349479

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RIG-I inhibits pancreatic β cell proliferation through competitive binding of activated Src.

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RIG-I inhibits pancreatic β cell proliferation through competitive binding of activated Src.

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