Elevated fasting insulin concentrations associate with impaired insulin signaling in skeletal muscle of healthy subjects independent of obesity

• Published in: Diabetes/metabolism research and reviews 2002-05, Vol.18 (3), p.209-216
• Main Authors: Korsheninnikova, Elena, Seppälä-Lindroos, Anneli, Vehkavaara, Satu, Goto, Takashi, Virkamäki, Antti
• Format: Article
• Language: English
• Subjects: Adult; Animals; Biological and medical sciences; Biopsy; Blood Glucose - metabolism; Body Mass Index; diabetes; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting; Freeze Drying; Glucose Clamp Technique; human; Humans; Insulin - blood; Insulin - pharmacology; Insulin - physiology; insulin resistance; Male; Medical sciences; methods; Models, Animal; Muscle, Skeletal - cytology; Muscle, Skeletal - physiology; Muscle, Skeletal - physiopathology; Obesity - physiopathology; Phosphatidylinositol 3-Kinases - drug effects; Phosphatidylinositol 3-Kinases - metabolism; Rats; Rats, Wistar; Reference Values; Regression Analysis; Signal Transduction
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.272

Background Insulin signaling is impaired in the skeletal muscle of obese subjects but whether defects in skeletal muscle insulin signaling also characterize insulin resistance of non‐obese individuals is unknown. The detection of insulin signaling defects in muscle biopsies is hampered by thevariation of the contaminating non‐muscle elements such as blood, connective tissue, fat, and blood vessel structures. Freeze‐drying and macroscopic purification of the muscle fibers prior to the analysis might offer a possibility to minimize the analytical variation due to these contaminants. Methods In the present study we first determined whether insulin signaling could be reliably assessed in freeze‐dried muscle specimens, which are free ofnon‐muscle contaminants, and then applied this method to the study of insulin signaling in weight‐matched insulin‐sensitive and insulin‐resistant non‐diabetic men. Results In rat muscle, increases in tyrosine phosphorylation of insulin receptor (IR) and activity of the insulin receptor substrate‐1 (IRS‐1)‐associated phosphatidylinositol (PI) 3‐kinase activity by insulin were similar or higher in freeze‐dried and purified muscle than wet muscle. Prior to freeze‐drying and purification, biopsies of human vastus lateralis muscle contained between 1% and 40% non‐muscle contaminants (11±3%, mean±SEM, n=19). In freeze‐dried biopsies of human vastus lateralis muscle taken before and after 30 min of hyperinsulinemia (serum free insulin 61±1 mU/l) in 13 non‐diabetic men, insulin increased IR tyrosine phosphorylation 1.4‐fold (p