Comparison of vascular relaxation, lipolysis and glucose uptake by peroxisome proliferator-activated receptor-γ activation in + db/+ m and + db/+ db mice

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Journal Article

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Peroxisome proliferator-activated receptor-γ, Aortic relaxation, Lipolysis, Glucose uptake, + db/+ db mice




In this study, we determined the in vitro effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation on the aortic relaxation, lipolysis and insulin-induced [3H]-glucose uptake of the abdominal (omental) adipocytes of the non-diabetic (+ db/+ m) and obese/diabetic (+ db/+ db) mice. The expression of PPAR-γ (mRNA and protein) in aorta and adipose tissues was evaluated and compared. Cumulative application of ciglitazone, pioglitazone and troglitazone (PPAR-γ agonists) caused a concentration-dependent aortic relaxation (sensitive to 2-chloro-5-nitro-N-phenylbenzamide (GW9662) (1 μM, a selective PPAR-γ antagonist) and Nω-nitro-l-arginine methyl ester (l-NAME) (20 μM, a nitric oxide synthase inhibitor)) with a maximum relaxation of ∼ 30% (3 μM) in + db/+ m mice, whereas no relaxation was observed in + db/+ db mice. All PPAR-γ 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 μM) caused an enhancement of [3H]-glucose uptake into adipocytes with a greater magnitude in + db/+ m mice. In contrast, none of the PPAR-γ agonists tested (0.1, 1 and 10 μM) altered the basal and the insulin (0.1 μM)-induced [3H]-glucose uptake into adipocytes of both species. In addition, there was no difference in PPAR-γ expression (mRNA and protein) in the aorta and adipose tissues between the species. In conclusion, our results demonstrate that PPAR-γ is present in the abdominal (omental) adipose tissue and thoracic aorta. An acute activation of PPAR-γ produced a small (∼ 30%) aortic relaxation (nitric oxide/endothelium-dependent) of + db/+ m mice. However, all PPAR-γ agonists examined have no acute effect on lipolysis and the insulin-induced glucose uptake into adipocytes of both + db/+ m and + db/+ db mice.

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European Journal of Pharmacology

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