Insulin Receptor Substrate 1의 세린731 인산화 억제를 통한 살리실산의 인슐린저항성 개선효과 기전

Salicylate Enhances Insulin Signaling by Preventing Ser731 Phosphorylation of Insulin Receptor Substrate 1

Salicylate (SA) was shown to alleviate insulin resistance. Here, we showed that SA inhibited Ser731 phosphorylation of insulin receptor substrate (IRS1) and S6 kinase activation, and enhanced tyrosinase phosphorylation of IRS1 in response to insulin or amino acid. Experiments using a cJun N-terminal kinase (JNK)-deficient cell and an IRS1 JNK-binding mutant showed that JNK is not required for Ser731 phosphorylation. A two-week treatment of obese mice with SA resulted in decreased Ser731 phosphorylation and enhanced insulin signaling. These results suggest that SA enhanced insulin signaling by inhibiting Ser731 phosphorylation of IRS1.