A novel IRS-1-associated protein, DGK? regulates GLUT4 translocation in 3T3-L1 adipocytes.

ABSTRACT: Insulin receptor substrates (IRSs) are major targets of insulin receptor tyrosine kinases. Here we identified diacylglycerol kinase zeta (DGK?) as an IRS-1-associated protein, and examined roles of DGK? in glucose transporter 4 (GLUT4) translocation to the plasma membrane. When DGK? was knocked-down in 3T3-L1 adipocytes, insulin-induced GLUT4 translocation was inhibited without affecting other mediators of insulin-dependent signaling. Similarly, knockdown of phosphatidylinositol 4-phosphate 5-kinase 1? (PIP5K1?), which had been reported to interact with DGK?, also inhibited insulin-induced GLUT4 translocation. Moreover, DGK? interacted with IRS-1 without insulin stimulation, but insulin stimulation decreased this interaction. Over-expression of sDGK? (short-form DGK?), which competed out DGK? from IRS-1, enhanced GLUT4 translocation without insulin stimulation. Taking these results together with the data showing that cellular PIP5K activity was correlated with GLUT4 translocation ability, we concluded that IRS-1-associated DGK? prevents GLUT4 translocation in the absence of insulin and that the DGK? dissociated from IRS-1 by insulin stimulation enhances GLUT4 translocation through PIP5K1? activity.

SUBMITTER: Liu T 

PROVIDER: S-EPMC5064357 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature