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Knockdown of endogenous SKIP gene enhanced insulin-induced glycogen synthesis signaling in differentiating C2C12 myoblasts

  • Xiong, Qi (Key Laboratory of Swine Breeding and Genetics, Ministry of Agriculture, College of Animal Science and Technology, HuazhongAgricultural University) ;
  • Deng, Chang-Yan (Key Laboratory of Swine Breeding and Genetics, Ministry of Agriculture, College of Animal Science and Technology, HuazhongAgricultural University) ;
  • Chai, Jin (Key Laboratory of Swine Breeding and Genetics, Ministry of Agriculture, College of Animal Science and Technology, HuazhongAgricultural University) ;
  • Jiang, Si-Wen (Key Laboratory of Swine Breeding and Genetics, Ministry of Agriculture, College of Animal Science and Technology, HuazhongAgricultural University) ;
  • Xiong, Yuan-Zhu (Key Laboratory of Swine Breeding and Genetics, Ministry of Agriculture, College of Animal Science and Technology, HuazhongAgricultural University) ;
  • Li, Feng-E (Key Laboratory of Swine Breeding and Genetics, Ministry of Agriculture, College of Animal Science and Technology, HuazhongAgricultural University) ;
  • Zheng, Rong (Key Laboratory of Swine Breeding and Genetics, Ministry of Agriculture, College of Animal Science and Technology, HuazhongAgricultural University)
  • Published : 2009.02.28

Abstract

PI(3,4,5)$P_3$ produced by the activated PI3-kinase is a key lipid second messenger in cell signaling downstream of insulin. Skeletal muscle and kidney-enriched inositol phosphatase (SKIP) identified as a 5'-inositol phosphatase that hydrolyzes PI(3,4,5) $P_3$ to PI(3,4)$P_2$, negatively regulates the insulin-induced glycogen synthesis in skeletal muscle. However the mechanism by which this occurs remains unclear. To elucidate the function of SKIP in glycogen synthesis, we employed RNAi techniques to knockdown the SKIP gene in differentiating C2C12 myoblasts. Insulininduced phosphorylation of Akt (protein kinase B) and GSK-3$\beta$ (Glycogen synthase kinase), subsequent dephosphorylation of glycogen synthase and glycogen synthesis were increased by inhibiting the expression of SKIP, whereas the insulin-induced glycogen synthesis was decreased by overexpression of WT-SKIP. Our results suggest that SKIP plays a negative regulatory role in Akt/ GSK-3$\beta$/GS (glycogen synthase) pathway leading to glycogen synthesis in myocytes.

Keywords

Akt;Glycogen synthase;GSK3$\beta$;RNAi;SKIP

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