Telmisartan, an angiotensin II type 1 receptor blocker, inhibits advanced glycation end-product (AGE)-elicited hepatic insulin resistance via peroxisome proliferator-activated receptor-gamma activation

J Int Med Res. 2008 Mar-Apr;36(2):237-43. doi: 10.1177/147323000803600204.

Abstract

This study examined whether telmisartan, a unique angiotensin II type 1 receptor blocker (ARB) with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity, improved insulin resistance in advanced glycation end-product (AGE)-exposed human hepatoma (Hep3B) cells. AGE increased phosphorylation of insulin receptor substrate-1 (IRS-1) at serine-307 residues in Hep3B cells. It also decreased tyrosine phosphorylation of IRS-1 and, subsequently, reduced the association of the p85 subunit of phosphatidylinositol 3-kinase with IRS-1 and glycogen synthesis in insulin-exposed Hep3B cells, all of which were inhibited by telmisartan. The insulin-sensitizing properties of telmisartan in AGE-exposed Hep3B cells were significantly blocked by GW9662, an inhibitor of PPAR-gamma. Candesartan, another ARB, did not affect AGEs-induced serine phosphorylation of IRS-1 at serine-307 residues in Hep3B cells. Our study suggests that telmisartan could improve AGE-elicited insulin resistance in Hep3B cells by inhibiting serine phosphorylation of IRS-1, at least in part, via activation of PPAR-gamma. Telmisartan may play a protective role against hepatic insulin resistance in diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Benzimidazoles / pharmacology*
  • Benzoates / pharmacology*
  • Cell Line, Tumor
  • Glycation End Products, Advanced / antagonists & inhibitors*
  • Glycation End Products, Advanced / physiology*
  • Humans
  • Insulin / physiology
  • Insulin Resistance / physiology*
  • Liver / drug effects*
  • Liver / metabolism*
  • PPAR gamma / metabolism*
  • PPAR gamma / physiology
  • Receptor, Angiotensin, Type 1 / metabolism
  • Telmisartan

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Benzoates
  • Glycation End Products, Advanced
  • Insulin
  • PPAR gamma
  • Receptor, Angiotensin, Type 1
  • Telmisartan