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Sci Rep. 2016 Jun 28;6:28914. doi: 10.1038/srep28914.

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

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Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, PR China.
Department of Anesthesiology, Huaian First People's Hospital, Nanjing Medical University, Huaian, Jiangsu, PR China.
Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, PR China.
The Pre-clinical Medicine College, Nanjing University of Chinese Medicine, Nanjing, PR China.
Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing, PR China.


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.

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