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.
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.
Yoshida
T
T
Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Yamagishi
S
S
Matsui
T
T
Nakamura
K
K
Ueno
T
T
Takeuchi
M
M
Sata
M
M
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism* / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D017127:Glycation End Products, Advanced; D007328:Insulin; D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1; D000077333:Telmisartan