Insulin signal transduction in skeletal muscle from glucose-intolerant relatives of type 2 diabetic patients [corrected]
| Autor: | H, Storgaard, X M, Song, C B, Jensen, S, Madsbad, M, Björnholm, A, Vaag, J R, Zierath |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Blood Glucose Male Biopsy Middle Aged Protein Serine-Threonine Kinases Phosphoproteins Body Mass Index Phosphatidylinositol 3-Kinases Diabetes Mellitus Type 2 Proto-Oncogene Proteins Glucose Intolerance Glucose Clamp Technique Insulin Receptor Substrate Proteins Humans Insulin Lipid Peroxidation Insulin Resistance Phosphorylation Muscle Skeletal Phosphotyrosine Oxidation-Reduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Diabetes. 50(12) |
| ISSN: | 0012-1797 |
| Popis: | To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects before and during a euglycemic-hyperinsulinemic clamp. IGT relatives were insulin-resistant in oxidative and nonoxidative pathways for glucose metabolism. In vivo insulin infusion increased skeletal muscle insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (P = 0.01) and phosphatidylinositide 3-kinase (PI 3-kinase) activity (phosphotyrosine and IRS-1 associated) in control subjects (P0.02) but not in IGT relatives (NS). The incremental increase in insulin action on IRS-1 tyrosine phosphorylation was lower in IGT relatives versus control subjects (P0.05). The incremental defects in signal transduction noted for IRS-1 and PI 3-kinase may be attributed to elevated basal phosphorylation/activity of these parameters, because absolute phosphorylation/activity under insulin-stimulated conditions was similar between IGT relatives and control subjects. Insulin increased Akt serine phosphorylation in control subjects and IGT relatives, with a tendency for reduced phosphorylation in IGT relatives (P = 0.12). In conclusion, aberrant phosphorylation/activity of IRS-1, PI 3-kinase, and Akt is observed in skeletal muscle from relatives of patients with type 2 diabetes with IGT. However, the elevated basal activity of these signaling intermediates and the lack of a strong correlation between these parameters to glucose metabolism suggests that other defects of insulin signal transduction and/or downstream components of glucose metabolism may play a greater role in the development of insulin resistance in skeletal muscle from relatives of patients with type 2 diabetes. |
| Databáze: | OpenAIRE |
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