Comparison of vascular relaxation, lipolysis and glucose uptake by peroxisome proliferator-activated receptor-gamma activation in +db/+m and +db/+db mice.
In this study, we determined the in vitro effect of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation on the aortic relaxation, lipolysis and insulin-induced [(3)H]-glucose uptake of the abdominal (omental) adipocytes of the non-diabetic (+db/+m) and obese/diabetic (+db/+db) mice. The expression of PPAR-gamma (mRNA and protein) in aorta and adipose tissues was evaluated and compared. Cumulative application of ciglitazone, pioglitazone and troglitazone (PPAR-gamma agonists) caused a concentration-dependent aortic relaxation (sensitive to 2-chloro-5-nitro-N-phenylbenzamide (GW9662) (1 microM, a selective PPAR-gamma antagonist) and N(omega)-nitro-l-arginine methyl ester (l-NAME) (20 microM, a nitric oxide synthase inhibitor)) with a maximum relaxation of approximately 30% (3 microM) in +db/+m mice, whereas no relaxation was observed in +db/+db mice. All PPAR-gamma agonists examined did not alter the basal lipolysis of both species, but forskolin caused a concentration-dependent lipolysis, with a greater magnitude observed in +db/+m mice. Insulin (0.1 and 1 microM) caused an enhancement of [(3)H]-glucose uptake into adipocytes with a greater magnitude in +db/+m mice. In contrast, none of the PPAR-gamma agonists tested (0.1, 1 and 10 microM) altered the basal and the insulin (0.1 microM)-induced [(3)H]-glucose uptake into adipocytes of both species. In addition, there was no difference in PPAR-gamma expression (mRNA and protein) in the aorta and adipose tissues between the species. In conclusion, our results demonstrate that PPAR-gamma is present in the abdominal (omental) adipose tissue and thoracic aorta. An acute activation of PPAR-gamma produced a small ( approximately 30%) aortic relaxation (nitric oxide/endothelium-dependent) of +db/+m mice. However, all PPAR-gamma agonists examined have no acute effect on lipolysis and the insulin-induced glucose uptake into adipocytes of both +db/+m and +db/+db mice.
Seto
Sai Wang
SW
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Lam
Tsz Yan
TY
Leung
George P H
GP
Au
Alice L S
AL
Ngai
Sai Ming
SM
Chan
Shun Wan
SW
Kwan
Yiu Wa
YW
D050153:Abdominal Fat / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology*; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D047495:PPAR gamma / Q000819:agonists* / Q000096:biosynthesis; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000819:agonists / Q000096:biosynthesis; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D014664:Vasodilation / Q000187:drug effects
D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077288:Troglitazone; D005947:Glucose; C039671:ciglitazone; D000077205:Pioglitazone