Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects.
We evaluated the effects of rosiglitazone (4 mg b.i.d.) and metformin (1 g b.i.d.) monotherapy for 26 weeks on adipose tissue insulin-stimulated glucose uptake in patients (n = 41) with type 2 diabetes. Before and after the treatment, glucose uptake was measured using 2-[(18)F]fluoro-2-deoxyglucose and positron emission tomography and adipose tissue masses were quantified using magnetic resonance imaging. Rosiglitazone improved insulin-stimulated whole-body glucose uptake by 44% (P < 0.01 vs. placebo). Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2.0 kg in the metformin group (P < 0.05 vs. placebo). In visceral adipose tissue, glucose uptake increased by 29% (from 17.8 +/- 2.0 to 23.0 +/- 2.6 micro mol x kg(-1) x min(-1), P < 0.05 vs. placebo) in the rosiglitazone group but to a lesser extent (17%) in the metformin group (from 16.2 +/- 1.5 to 18.9 +/- 1.7 micro mol x kg(-1) x min(-1), P < 0.05 vs. baseline). Because the visceral adipose tissue mass simultaneously decreased with both treatments (P < 0.05), no change was observed in total visceral glucose uptake per depot. Rosiglitazone significantly enhanced glucose uptake in the femoral subcutaneous area, either when expressed per tissue mass (from 10.8 +/- 1.2 to 17.1 +/- 1.7 micro mol x kg(-1) x min(-1), P < 0.01 vs. placebo) or per whole-fat depot (P < 0.05 vs. placebo). In conclusion, metformin treatment resulted in improvement of glycemic control without enhancement of peripheral insulin sensitivity. The improved insulin sensitivity of the nonabdominal subcutaneous adipose tissue during treatment with rosiglitazone partly explains the enhanced whole-body insulin sensitivity and underlies the central role of adipose tissue for action of peroxisome proliferator-activated receptor gamma agonist in vivo.
Virtanen
Kirsi A
KA
Turku PET Centre, University of Turku and Turku University Hospital, Finland.
Hällsten
Kirsti
K
Parkkola
Riitta
R
Janatuinen
Tuula
T
Lönnqvist
Fredrik
F
Viljanen
Tapio
T
Rönnemaa
Tapani
T
Knuuti
Juhani
J
Huupponen
Risto
R
Lönnroth
Peter
P
Nuutila
Pirjo
P
D000273:Adipose Tissue / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000502:physiology; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D000077154:Rosiglitazone; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D014055:Tomography, Emission-Computed; D015431:Weight Loss
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D007773:Lactates; D008055:Lipids; D010919:Placebos; D019275:Radiopharmaceuticals; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019788:Fluorodeoxyglucose F18; D008687:Metformin; D005947:Glucose