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

Qi Xiong, Chang-Yan Deng, Jin Chai, Si-Wen Jiang, Yuan-Zhu Xiong, Feng-E Li, Rong Zheng
2009 BMB Reports  
PI(3,4,5)P3 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) P3 to PI(3,4)P2, 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
more » ... Ai techniques to knockdown the SKIP gene in differentiating C2C12 myoblasts. Insulininduced phosphorylation of Akt (protein kinase B) and GSK-3β (Glycogen synthase kinase), subsequent dephosphorylation of glycogen synthase and glycogen synthesis were increased by in hibiting 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-3β/GS (glycogen synthase) pathway leading to glycogen synthesis in myocytes. [BMB reports 2009; 42(2): 119-124]
doi:10.5483/bmbrep.2009.42.2.119 pmid:19250614 fatcat:xm5jybhdrvfflia4ulb2zet7fe