Global IRS-1 phosphorylation analysis in insulin resistance.

ABSTRACT: IRS-1 serine phosphorylation is often elevated in insulin resistance models, but confirmation in vivo in humans is lacking. We therefore analysed IRS-1 phosphorylation in human muscle in vivo.We used HPLC-electrospray ionisation (ESI)-MS/MS to quantify IRS-1 phosphorylation basally and after insulin infusion in vastus lateralis muscle from lean healthy, obese non-diabetic and type 2 diabetic volunteers.Basal Ser323 phosphorylation was increased in type 2 diabetic patients (2.1?±?0.43, p???0.05, fold change vs lean controls). Thr495 phosphorylation was decreased in type 2 diabetic patients (p???0.05). Insulin increased IRS-1 phosphorylation at Ser527 (1.4?±?0.17, p???0.01, fold change, 60 min after insulin infusion vs basal) and Ser531 (1.3?±?0.16, p???0.01, fold change, 60 min after insulin infusion vs basal) in the lean controls and suppressed phosphorylation at Ser348 (0.56?±?0.11, p???0.01, fold change, 240 min after insulin infusion vs basal), Thr446 (0.64?±?0.16, p???0.05, fold change, 60 min after insulin infusion vs basal), Ser1100 (0.77?±?0.22, p???0.05, fold change, 240 min after insulin infusion vs basal) and Ser1142 (1.3?±?0.2, p???0.05, fold change, 60 min after insulin infusion vs basal).We conclude that, unlike some aspects of insulin signalling, the ability of insulin to increase or suppress certain IRS-1 phosphorylation sites is intact in insulin resistance. However, some IRS-1 phosphorylation sites do not respond to insulin, whereas other Ser/Thr phosphorylation sites are either increased or decreased in insulin resistance.

SUBMITTER: Langlais P 

PROVIDER: S-EPMC3882165 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature