Telmisartan increases localization of glucose transporter 4 to the plasma membrane and increases glucose uptake via peroxisome proliferator-activated receptor γ in 3T3-L1 adipocytes

Angiotensin Ills a peptide hormone with strong vasoconstrictive action, and recent reports have shown that Angiotensin II receptor type 1 antagonists (angiotensin II receptor blockers) also improve glucose metabolism. The angiotensin II receptor blocker telmisartan acts as an agonistic ligand of the peroxisome proliferator-activated receptor gamma (PPAR gamma). In this study, we investigated the effects of telmisartan on glucose uptake and insulin sensitivity in 3T3-L1 adipocytes and compared it with the action of other angiotensin II receptor blockers. Telmisartan treatment dose-dependently increased (from 1 mu M) protein expression of PPAR gamma-regulated molecules such as fatty acid binding protein 4 (FABP4), insulin receptor, and glucose transporter 4 (GLUT4). Telmisartan increased glucose uptake both with and without insulin stimulation in 3T3-L1 adipocytes. Telmisartan increased the up-regulation of phosphorylated insulin receptor, insulin receptor substrate-1 (IRS-1) and Akt by insulin, suggesting that telmisartan increases insulin sensitivity. Furthermore, in the absence of insulin, telmisartan, but not candesartan, increased GLUT4 levels at the plasma membrane. These effects by 10 AM telmisartan were similar potency to those of 1 mu M troglitazone, an activator of PPAR gamma. In addition, up-regulation of glucose uptake by telmisartan was inhibited by a PPAR gamma antagonist, T0070907 (2-chloro-5-nitro-N-4-pyridinyl-benzamide). These results indicate that telmisartan acts via PPAR gamma activation in adipose tissue and may be an effective therapy for the metabolic syndrome. (C) 2011 Elsevier B.V. All rights reserved.