Rosiglitazone improves insulin resistance, lipid profile and promotes adiposity in a genetic model of metabolic syndrome X.
RSG is a member of the TZD group of drugs widely used in treatment of type 2 diabetes. The underlying mechanism of TZD action in insulin-sensitive tissues is not fully understood. In this study we show that 14-day RSG administration in a new rodent model of metabolic syndrome X, polydactylous rat strain (PD/Cub), substantially improves its lipid profile (serum TGs 4.20 +/- 0.23 vs 2.34 +/- 0.14 mmol/l, P < 0.0001; FFA 0.46 +/- 0.05 vs 0.33 +/- 0.02 mmol/l, P = 0.017), diminishes the liver TG depots (15.76 +/- 0.60 vs 8.44 +/- 0.55 micromol/g, P < 0.0001), serum insulin concentrations (1.10 +/- 0.08 vs 0.63 +/- 0.02 nmol/l, P < 0.0001) and promotes visceral adiposity (adiposity index 1.28 +/- 0.03 vs 1.85 +/- 0.07, P < 0.0001). No changes were observed in serum or liver concentrations of cholesterol. Concomitantly, both basal and insulin-stimulated glycogen synthesis in red-fibre type muscle (m. soleus) was enhanced, as well as glucose uptake into adipose tissue. However, glucose oxidation in soleus (basal and insulin-stimulated) remained unchanged. In consent with previously published data we suggest the current pharmacogenetic study as a further proof of substantial influence of genetic background on the physiological outcome of TZD therapy.
Seda
O
O
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Kazdová
L
L
Krenová
D
D
Kren
V
V
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D006003:Glycogen; D005947:Glucose