title: Acute exposure to rosiglitazone does not affect glucose transport in intact human skeletal muscle.
abstract: 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/m(2)). Skeletal muscle strips were isolated and exposed to rosiglitazone (1 or 10 micromol/L), 5-aminoimidazole-4-carboxamide 1-beta-D-ribonucleoside (1 mmol/L), insulin (120 nmol/L), or a combination of insulin (120 nmol/L) and rosiglitazone (10 micromol/L) in vitro for 1 hour. Glucose transport was analyzed by accumulation of intracellular 3-O-methyl [(3)H] glucose; phosphorylation of Akt-Ser(473) and Akt-Thr(308) and phosphorylation of acetyl coenzyme A carboxylase beta were determined using phosphospecific antibodies. 5-Aminoimidazole-4-carboxamide 1-beta-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 beta, 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-Ser(473) or Akt-Thr(308) in isolated muscle strips. In conclusion, acute exposure to rosiglitazone does not affect glucose transport in human skeletal muscle.
authors.affiliation: Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, 00290 Helsinki, Finland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Skrobuk
authors.forename: Heidi
authors.initials: H
authors.lastname: Kuoppamaa
authors.forename: Anne
authors.initials: A
authors.lastname: Hiukka
authors.forename: Heikki A
authors.initials: HA
authors.lastname: Koistinen
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001823:Body Composition; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010101:Oxygen Consumption; D010766:Phosphorylation / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000103:Acetyl-CoA Carboxylase; D005947:Glucose