Globular adiponectin stimulates glucose transport in type 2 diabetic muscle

Background Adiponectin acts as an insulin sensitizer in rodent models. The direct effect of adiponectin in intact type 2 diabetic muscle is unknown. We examined whether adiponectin stimulates glucose transport in isolated skeletal muscle strips from type 2 diabetic men. Methods We obtained open muscle biopsies from 12 men with type 2 diabetes (56 ± 1 years, 30.5 ± 1.1 kg/m 2 ), and from 15 non‐diabetic men (59 ± 1 years, 28.0 ± 1.0 kg/m 2 ). Skeletal muscle strips were isolated and exposed to globular adiponectin (2.5 µg/mL), insulin (120 n M ) and/or AICAR (1 m M ) in vitro for 1 h. Glucose transport was analysed by accumulation of intracellular 3‐ O ‐methyl [ 3 H] glucose, phosphorylation of Akt‐Ser 473 and Akt‐Thr 308 was determined using phosphospecific antibodies, and adiponectin receptor 1 and 2 content was measured using specific antibodies. Results Globular adiponectin increased glucose transport rate by 1.3‐fold ( P < 0.01) in type 2 diabetic, but not in non‐diabetic muscle. Insulin‐stimulated glucose transport rate was unaltered by exposure to globular adiponectin in either group. AICAR increased glucose transport and enhanced insulin‐stimulated glucose transport in type 2 diabetic and non‐diabetic muscles. Insulin‐stimulated phosphorylation of Akt‐Ser 473 or Akt‐Thr 308 was comparable in type 2 diabetic and non‐diabetic muscles, and unaltered by the addition of globular adiponectin in either group. Adiponectin receptor expression was similar in skeletal muscle from type 2 diabetic and non‐diabetic men. Conclusions Globular adiponectin directly increases glucose transport in skeletal muscle from type 2 diabetic patients. This may occur via Akt‐independent signalling routes. Copyright © 2008 John Wiley & Sons, Ltd.