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

Eur J Pharmacol. 2007 Oct 15;572(1):40-8. doi: 10.1016/j.ejphar.2007.05.070. Epub 2007 Jun 14.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat / metabolism
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiopathology*
  • Carbohydrate Metabolism / drug effects
  • Chromans / pharmacology
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology*
  • Female
  • Glucose / metabolism*
  • Hypoglycemic Agents / pharmacology
  • In Vitro Techniques
  • Insulin / pharmacology
  • Lipid Metabolism
  • Lipolysis / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Obesity / metabolism
  • Obesity / physiopathology
  • PPAR gamma / agonists*
  • PPAR gamma / biosynthesis
  • Pioglitazone
  • RNA, Messenger / agonists
  • RNA, Messenger / biosynthesis
  • Thiazolidinediones / pharmacology
  • Troglitazone
  • Vasodilation / drug effects


  • Chromans
  • Hypoglycemic Agents
  • Insulin
  • PPAR gamma
  • RNA, Messenger
  • Thiazolidinediones
  • Troglitazone
  • Glucose
  • ciglitazone
  • Pioglitazone