In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a novel serine kinase in insulin-resistant rodents

摘要: Abstract Insulin resistance is a key pathophysiologic feature of obesity and type 2 diabetes associated with other human diseases, including atherosclerosis, hypertension, hyperlipidemia, polycystic ovarian disease. Yet, the specific cellular defects that cause insulin are not precisely known. receptor substrate (IRS) proteins important signaling molecules mediate action in insulin-sensitive cells. Recently, serine phosphorylation IRS has been implicated attenuating thought to be potential mechanism for resistance. However, vivo increased insulin-resistant animal models reported before. In present study, we have confirmed previous findings both JCR:LA-cp Zucker fatty rats, two genetically unrelated rodent models, an enhanced kinase activity liver The specifically phosphorylates conserved Ser789 residue IRS-1, which sequence motif separate from ones MAPK, c-Jun N-terminal kinase, glycogen-synthase 3 (GSK-3), Akt, phosphatidylinositol 3′-kinase, or casein kinase. It similar AMP-activated protein but animals was shown suggesting novel Using antibody against Ser(P)789peptide then demonstrated first time striking increase Ser789-phosphorylated IRS-1 livers indicating vivo. Taken together, these data strongly suggest unknown Ser789phosphorylation may play role models.