Correlation of the insulin receptor substrate-1 with insulin-responsive deoxyglucose transport in 3T3-L1 adipocytes.

We have devised procedures for decreasing the amount of IRS-1 in 3T3-L1 adipocytes (viz., chronic treatments with insulin, dexamethasone, 1-methyl-3-isobutylxanthine, cycloheximide or actinomycin D) and have determined the correlation between the amounts of IRS-1, insulin receptor, GluT4 and phosphatidylinositol 3'-kinase regulatory subunit with insulin-responsive dGlc transport. Each of these treatments decreased insulin responsiveness that correlated with the amount of IRS-1, but not with the amount of the other signaling proteins or tyrosine-phosphorylated IRS-1. Removal of insulin after chronic treatment resulted in a return of both insulin responsiveness and IRS-1. Increased expression of IRS-1 occurred during differentiation simultaneously with increased insulin-responsive dGlc transport. These data are consistent with a role of IRS-1 in insulin signaling to the glucose transport system.