Insulin and metabolic stress stimulate multisite serine/threonine phosphorylation of insulin receptor substrate 1 and inhibit tyrosine phosphorylation

Abstract

Background: Metabolic stresses, including hyperinsulinemia, promote insulin resistance. Results: Monoclonal antibodies raised against Ser(P)/Thr(P) residues in IRS1 were used to quantify phosphorylation in response to insulin or agents that model metabolic stress. Conclusion: Similar IRS1 Ser(P)/Thr(P) residues are increased by insulin or metabolic stress, and some correlate significantly with reduced IRS1 tyrosine phosphorylation. Significance: Metabolic stress co-opts insulin-dependent IRS1 phosphorylation to aggravate insulin resistance. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.