Angiotensin inhibition stimulates PPARγ and the release of visfatin


Michael Wolzt, MD, Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Wien, Austria. Tel.: +431404002981; fax: +431404002998; e-mail:


Background  Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) exhibit beneficial antidiabetic effects in patients with type 2 diabetes independent of their blood pressure-lowering effects. Some antidiabetic properties of ARB and ACE-I might by exerted by activation of peroxisome proliferator-activated receptor gamma (PPARγ). However, it is not clear whether this action is drug specific.

Materials and methods  The binding affinity of telmisartan, valsartan, lisinopril, rosiglitazone and angiotensin II to PPARγ was assessed in a cell-free assay system. PPARγ signalling was studied in isolated skeletal muscle cells using Western blot analysis of phosphorylated protein kinase B (pAKT) and phosphorylated insulin like growth factor-1 receptor (pILGF-1R). Further, the ability of the drugs under study to stimulate the release of the adipocytokine visfatin was investigated in isolated human adipocytes, skeletal muscle cells, and umbilical vein endothelial cells (HUVEC).

Results  The binding affinity to PPARγ was highest for telmisartan with a half-maximal effective concentration of 463 nM, followed by lisinopril (2·9 µM) and valsartan (6·2 µM). In skeletal muscle cells phosphorylation of ILGF-1R was 2-fold increased after incubation with telmisartan or valsartan and 1·7-fold with lisinopril. pAKT expression was enhanced after incubation with telmisartan, valsartan and with lisinopril. The release of visfatin from adipocytes was 1·6-fold increased after treatment with lisinopril and about 2·0-fold increased with telmisartan and valsartan. Similar results were obtained in skeletal muscle cells and HUVEC.

Conclusions  Our data confirm agonism of telmisartan, valsartan and lisinopril on PPARγ. Pharmacokinetic differences may explain different potencies of PPARγ stimulation by drugs acting on the renin-angiotensin system in clinical settings.