Thiazolidinediones exert different effects on insulin resistance between dexamethasone-treated rats and wistar fatty rats.
We determined the in vivo effects of thiazolidinediones on insulin resistance induced by dexamethasone (Dx), as well as that observed in Wistar fatty (WF) rats, using glucose clamp technique to measure glucose uptake (Gu) and percent suppression of hepatic glucose output (HGOsup) to evaluate insulin resistance. Male Wistar rats were treated with Dx (0.5 mg/kg/day) for 7 days. Pioglitazone (P) or troglitazone (T) was coadministered orally for the same period at 10 and 200 mg/kg/day, respectively. Two, 5 and 20 mU/kg/min. of insulin infusion rates (IIR) were used. The Gu levels at clamp steady-state at IIR20 in rats treated with Dx (16.4 +/- 4.7 mg/kg/min.) were significantly lower than those in control rats (36.3 +/- 2.4). The Gu levels at the same IIR in rats coadminstered with P (19.6 +/- 3.2) and T (21.3 +/- 6.3) were slightly but significantly higher than that in rat treated with Dx. HGOsup at IIR5 in control rats (97.5 +/- 6.2%) was decreased by Dx treatment (52.1+/- 31.3). This decrease was slightly but significantly ameliorated by addition of T (78.3 +/- 12.2). The Gu levels at IIR20 in WF rats (6.6 +/- 0.9) were decreased significantly from that in lean littermates of WF (WL) rats (25.8 +/- 2.1). This attenuation of Gu increase was completely ameliorated with administration of P (20.9+/-2.8) or T (22.2+/-3.9). The HGOsup at IIR20 in WF rats (17.4 +/- 11.2) was significantly decreased from that in WL rats. Administration of P or T ameliorated this decrease completely. These results indicate that Dx induces insulin resistance by mechanisms different from those in WF rat, hence thiazolidinedione administration can be only partially useful to treat insulin resistance induced by Dx.
Kimura
M
M
The Third Department of Internal Medicine, Yamagata University School of Medicine, Japan.
Daimon
M
M
Tominaga
M
M
Manaka
H
H
Sasaki
H
H
Kato
T
T
D000818:Animals; D002839:Chromans / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004338:Drug Combinations; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism; D015309:Glucose Clamp Technique; D006706:Homeostasis; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D004338:Drug Combinations; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D003907:Dexamethasone; D000077288:Troglitazone; D005947:Glucose; D000077205:Pioglitazone