Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes: A case-control study

Background & aimsThe physiological regulation and contribution of the multiple phosphorylation sites insulin receptor substrate 1 (IRS1) to pathogenesis resistance is unknown. Our aims were map phosphorylated motifs IRS1 in skeletal muscle from people with normal glucose tolerance (NGT; n = 11) or type 2 diabetes mellitus (T2DM; 11).MethodsSkeletal biopsies obtained under fasted conditions during a euglycemic clamp identified by mass spectrometry.ResultsWe 33 individuals, including previously unreported ([Ser393] [Thr1017]). In men NGT T2DM, increased 5 peptides covering 10 serine threonine decreased 6 9 serine, tyrosine sites. Insulin-stimulation peptides, only NGT. Insulin T2DM.ConclusionsDespite severe resistance, pattern was not uniformly altered T2DM. results contribute evolving understanding signaling complement comprehensive