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

• Published in: Diabetes (New York, N.Y.) Vol. 47; no. 8; p. 1281
• Main Authors: Krook, A, Roth, RA, Jiang, XJ, Zierath, JR, Wallberg-Henriksson, H
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 1998
• Subjects: Medicin och hälsovetenskap
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.47.8.1281

Insulin-stimulated Akt kinase activity is reduced in skeletal muscle from NIDDM subjects. A Krook , R A Roth , X J Jiang , J R Zierath and H Wallberg-Henriksson Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden. ankr@klinfys.ks.se Abstract 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.