Insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle from NIDDM subjects after in vivo insulin stimulation

• Published in: Diabetes (New York, N.Y.) Vol. 46; no. 3; pp. 524 - 527
• Main Authors: BJÖRNHOLM, M, KAWANO, Y, LEHTIHET, M, ZIERATH, J. R
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.1997
• Subjects: 3-O-Methylglucose - metabolism; Biological and medical sciences; Biological Transport - drug effects; Biopsy; Complications and side effects; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Humans; Hyperinsulinism; Insulin; Insulin - pharmacology; Insulin Receptor Substrate Proteins; Insulin receptors; Medical sciences; Middle Aged; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Phosphatidylinositol; Phosphatidylinositol 3-Kinases; Phosphatidylinositols; Phosphoproteins - metabolism; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Phosphotyrosine - analysis; Physiological aspects; Receptors; Reference Values; Tumor Necrosis Factor-alpha - metabolism; Type 2 diabetes; Endocrinopathy; Human; Obesity; Pancreatic hormone; Phosphorylation; Enzyme; Transferases; Nutrition disorder; Striated muscle; Non insulin dependent diabetes; Insulin; 1-Phosphatidylinositol 3-kinase; Nutritional status; Hormonal receptor
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.46.3.524

We examined the effect of physiological hyperinsulinemia on insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and phosphatidylinositol (PI) 3-kinase activity in skeletal muscle from six lean-to-moderately obese NIDDM patients and six healthy subjects. A rise in serum insulin levels from approximately 60 to approximately 650 pmol/l increased IRS-1 tyrosine phosphorylation sixfold over basal levels in control muscle (P < 0.01), whereas no significant increase was noted in NIDDM muscle. The reduced IRS-1 phosphorylation in the NIDDM muscle was not related to changes in IRS-1 protein content, since IRS-1 protein expression was similar between control and NIDDM subjects (16.0 +/- 1.7 vs. 22.9 +/- 4.0 arbitrary units/mg protein for control and NIDDM, respectively; NS). Physiological hyperinsulinemia increased PI 3-kinase activity in control muscle twofold (P < 0.01), whereas no increase in insulin-stimulated PI 3-kinase activity was noted in the NIDDM muscle. Furthermore, in vitro insulin-stimulated (600 pmol/l) 3-O-methylglucose transport was 40% lower in isolated muscle from NIDDM subjects (P < 0.05). The present findings couple both reduced insulin-stimulated IRS-1 tyrosine phosphorylation and PI 3-kinase activity to the impaired insulin-stimulated glucose transport in skeletal muscle from lean-to-moderately obese NIDDM subjects.