Insulin-stimulated Akt kinase activity is reduced in skeletal muscle from NIDDM subjects

• Published in: Diabetes (New York, N.Y.) Vol. 47; no. 8; pp. 1281 - 1286
• Main Authors: KROOK, A, ROTH, R. A, XIN JIAN JIANG, ZIERATH, J. R, WALLBERG-HENRIKSSON, H
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.1998
• Subjects: Biological and medical sciences; Biological Transport - drug effects; Biopsy; Biosynthesis; Catheters; Diabetes; Diabetes Mellitus, Type 2 - enzymology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose; Glucose - metabolism; Humans; Insulin; Insulin - pharmacology; Insulin resistance; Kinases; Male; Medical sciences; Metabolism; Middle Aged; Muscle cells; Muscle, Skeletal - enzymology; Musculoskeletal system; Phosphorylation; Physiological aspects; Protein expression; Protein-Serine-Threonine Kinases; Proteins; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Reference Values; Synthesis; Type 2 diabetes; Endocrinopathy; Human; Enzymatic activity; Pathophysiology; Enzyme; Protein kinase; Transferases; Biological transport; Glucose; Striated muscle; Non insulin dependent diabetes
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.47.8.1281

The serine/threonine kinase Akt (PKB/Rac) has been implicated as playing a role in the insulin-signaling pathway to glucose transport. Little is known regarding the regulation of Akt kinase activity in insulin-sensitive tissues, such as skeletal muscle, or whether this regulation is altered in insulin-resistant states such as NIDDM. We examined the effect of insulin on Akt kinase activity in skeletal muscle from six NIDDM patients and six healthy subjects. Whole-body insulin sensitivity, assessed by the euglycemic-hyperinsulinemic clamp, was significantly lower in NIDDM subjects (P < 0.001), and this was accompanied by impaired in vitro insulin-stimulated glucose transport in skeletal muscle. In both groups, insulin induced a significant increase in Akt kinase activity, but the response to maximal insulin (60 nmol/l) was markedly reduced in skeletal muscle from NIDDM subjects (66% of control levels, P < 0.01). Impaired Akt kinase activity was not accompanied by decreased protein expression of Akt. Instead, a trend toward increased Akt expression was noted in skeletal muscle from NIDDM subjects (P < 0.1). These parallel defects in insulin-stimulated Akt kinase activity and glucose transport in diabetic skeletal muscle suggest that reduced Akt kinase activity may play a role in the development of insulin resistance in NIDDM.