IGF-I regulates IRS-1 expression in 3T3-L1 adipocytes

IRS-1 (the insulin receptor substrate-1) is required for signaling by both insulin and IGF-I. Chronic treatment of 3T3-L1 adipocytes with insulin at a ll concentrations results in increased proteolysis of IRS-1. In contrast, t reatment with low concentrations of IGF-I (EC50 = 625 pM) for 4 h caused an increase in IRS-1 to 170% of control. Actinomycin D and cycloheximide bloc ked the IGF-I effect, but not the insulin effect, suggesting that IG;F-I st imulated the synthesis of IRS-I. Concentrations of IGF-I high enough to cau se significant binding to the insulin receptor resulted in the down-regulat ion of IRS-I. Phosphatidylinositol 3'-kinase inhibitors blocked both the in sulin and IGF-I effects. Chronic TGF-I treatment caused an increase in both acute insulin-stimulated dGlc uptake and acute IGF-I-stimulated dGlc uptak e. Chronic insulin treatment caused a decrease in both acute insulin-stimul ated dGIc uptake and acute IGF-I-stimulated dGlc uptake. (C) 1999 Academic Press.