Global IRS-1 phosphorylation analysis in insulin resistance
| Autor: | Rebekka Mapes, Moulun Luo, E. Plummer, C. Meyer, Lawrence J. Mandarino, E. De Filippis, Jean Finlayson, M. Mattern, Paul R. Langlais, Zhengping Yi, P. Tongchinsub |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Threonine inorganic chemicals Spectrometry Mass Electrospray Ionization medicine.medical_specialty Insulin Receptor Substrate Proteins Endocrinology Diabetes and Metabolism medicine.medical_treatment macromolecular substances Type 2 diabetes environment and public health Article Quadriceps Muscle Serine Insulin resistance Tandem Mass Spectrometry In vivo Internal medicine Internal Medicine medicine Humans Hypoglycemic Agents Insulin Obesity Phosphorylation Infusions Intravenous Chromatography High Pressure Liquid Chemistry Middle Aged medicine.disease enzymes and coenzymes (carbohydrates) Endocrinology Diabetes Mellitus Type 2 bacteria Female Insulin Resistance Protein Processing Post-Translational |
| Zdroj: | Diabetologia. 54:2878-2889 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-011-2271-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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