title: 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.
abstract: Angiotensin II is 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 (PPARγ). 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 μM) protein expression of PPARγ-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 μM telmisartan were similar potency to those of 1 μM troglitazone, an activator of PPARγ. In addition, up-regulation of glucose uptake by telmisartan was inhibited by a PPARγ antagonist, T0070907 (2-chloro-5-nitro-N-4-pyridinyl-benzamide). These results indicate that telmisartan acts via PPARγ activation in adipose tissue and may be an effective therapy for the metabolic syndrome.
authors.affiliation: Department of Nutrition, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Furukawa
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mawatari
authors.forename: Kei
authors.initials: K
authors.lastname: Koyama
authors.forename: Sonoko
authors.initials: S
authors.lastname: Yasui
authors.forename: Ran
authors.initials: R
authors.lastname: Morizumi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Shimohata
authors.forename: Nagakatsu
authors.initials: N
authors.lastname: Harada
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D047495:PPAR gamma; D011972:Receptor, Insulin; D005947:Glucose; D000077333:Telmisartan