title: Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes.
abstract: Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone (P < 0.05) and metformin (P < 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% (P < 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% (P < 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1) improves insulin responsiveness in resting skeletal muscle and 2) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise.
authors.affiliation: Turku PET Centre, University of Turku, FIN-20521 Turku, Finland.
authors.forename: Kirsti
authors.initials: K
authors.lastname: Hällsten
authors.forename: Kirsi A
authors.initials: KA
authors.lastname: Virtanen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lönnqvist
authors.forename: Hannu
authors.initials: H
authors.lastname: Sipilä
authors.forename: Airi
authors.initials: A
authors.lastname: Oksanen
authors.forename: Tapio
authors.initials: T
authors.lastname: Viljanen
authors.forename: Tapani
authors.initials: T
authors.lastname: Rönnemaa
authors.forename: Jorma
authors.initials: J
authors.lastname: Viikari
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015444:Exercise / Q000502:physiology; D005215:Fasting / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007866:Leg; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011877:Radionuclide Imaging; D000077154:Rosiglitazone; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D045162:Thiazolidinediones
chemical_list: D001786:Blood Glucose; D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones