Acute exposure to rosiglitazone does not affect glucose transport in intact human skeletal muscle

Thiazolidinediones (TZDs) such as rosiglitazone are widely used as antidiabetic drugs. Animal studies suggest that TZDs may have direct metabolic actions in skeletal muscle. Here, we examined if acute exposure to rosiglitazone stimulates glucose transport rate and affects proximal insulin signaling in isolated skeletal muscle strips from nondiabetic men. Open muscle biopsies were obtained from musculus vastus lateralis from 15 nondiabetic men (50 ± 3 years old, 26.9 ± 1.1 kg/m2). Skeletal muscle strips were isolated and exposed to rosiglitazone (1 or 10 μmol/L), 5-aminoimidazole-4-carboxamide 1-β-d-ribonucleoside (1 mmol/L), insulin (120 nmol/L), or a combination of insulin (120 nmol/L) and rosiglitazone (10 μmol/L) in vitro for 1 hour. Glucose transport was analyzed by accumulation of intracellular 3-O-methyl [3H] glucose; phosphorylation of Akt-Ser473 and Akt-Thr308 and phosphorylation of acetyl coenzyme A carboxylase β were determined using phosphospecific antibodies. 5-Aminoimidazole-4-carboxamide 1-β-d-ribonucleoside and insulin increased glucose transport rate 1.5-fold (P < .05) and 1.7-fold (P < .01) in isolated muscle strips, respectively. Exposure to rosiglitazone transiently increased phosphorylation of acetyl coenzyme A carboxylase β, with a maximum effect at 15 minutes and return to baseline at 60 minutes. However, rosiglitazone did not affect basal or insulin-stimulated glucose transport rate, or phosphorylation of Akt-Ser473 or Akt-Thr308 in isolated muscle strips. In conclusion, acute exposure to rosiglitazone does not affect glucose transport in human skeletal muscle.