Molecular activation of PPARγ by angiotensin II type 1-receptor antagonists

Erbe, David V.; Gartrell, Katherine; Zhang, Yanling; Suri, Vipin; Kirincich, Steven J.; Will, Sarah; Perreault, Mylène; Wang, Suyue; Tobin, James F.

doi:10.1016/j.vph.2006.05.002

Cited by 125 publications

(116 citation statements)

References 27 publications

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“…In male SpragueDawley rats fed a high-fat, high carbohydrate diet for 3 months, telmisartan given along with the diet attenuated weight gain as well as glucose, insulin, and triglyceride levels (16,22). A recently published study questioned whether the reported effects of angiotensin receptor blockers on insulin sensitivity may occur through modulation of the nuclear receptor PPARγ (20). Telmisartan treatment resulted in significant PPARγ agonism in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Telmisartan treatment resulted in significant PPARγ agonism in vitro. However, when tested in vivo, telmisartan treatment had no effect on insulin sensitivity (20). The fructose-fed rat model is a commonly used model that mimics human MS in many aspects, including hypertension, hypertriglyceridemia, insulin resistance, and compensatory hyperinsulinemia, but it is not associated with obesity.…”

Section: Discussionmentioning

confidence: 99%

“…A few recent studies found that telmisartan, an angiotensin II type 1 (AT1) receptor antagonist, is a partial PPAR γ nuclear receptor agonist ( 16 -19 ). However, there are conflicting data regarding telmisartan's in vivo effects on metabolic parameters in animal models of the metabolic syndrome (16,20). Therefore, we assessed telmisartan's effects on adiponectin and metabolic indices in fructose-induced hypertensive, hyperinsulinemic, hyperlipidemic rats.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Telmisartan, Angiotensin II Receptor Antagonist, on Metabolic Profile in Fructose-Induced Hypertensive, Hyperinsulinemic, Hyperlipidemic Rats

et al. 2008

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The metabolic syndrome (MS) is a common risk factor for cardiovascular disease and type-2 diabetes.Recently, telmisartan, an angiotensin II receptor antagonist that has an antihypertensive effect, has been reported to be a partial peroxisome proliferator-activated receptor (PPAR ) agonist. The anti-diabetic hormone adiponectin has been recognized as a marker of in vivo PPAR activation. Therefore, we studied telmisartan's effect on the metabolic profile and adiponectin levels in a fructose-induced hypertensive, hyperinsulinemic, hyperlipidemic rat model. Twenty-four male Sprague-Dawley rats were divided into three groups (eight in each). One group of control rats was fed standard chow for 5 weeks while a second was fed a fructose-enriched diet. A third group was fed a fructose-enriched diet for 5 weeks and treated with telmisartan 5 mg/kg/day during the last 2 weeks. Fructose feeding increased systolic blood pressure (mean± SEM), from 130 ± 1 to 148 ± 2 mmHg, insulin from 0.26 ± 0.03 to 0.68 ± 0.08 ng/mL, and triglycerides from 102 ± 6 to 285 ± 23 mg/dL ( p < 0.05 for all variables). Telmisartan treatment reversed these effects and reduced blood pressure to 125 ± 2 mmHg, insulin levels to 0.41 ± 0.07 ng/mL, and triglycerides to 146 ± 18 mg/dL ( p < 0.05 for all variables), while attenuating the increase in body weight during weeks 3 to 5. In contrast, telmisartan did not affect plasma adiponectin levels. In conclusion, although telmisartan is considered a partial PPAR agonist, its beneficial effect in the fructose-induced hypertension, hypertriglyceridemia, and hyperinsulinemia rat model is apparently not mediated by adiponectin elevation but rather by direct inhibi-

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Telmisartan, Angiotensin II Receptor Antagonist, on Metabolic Profile in Fructose-Induced Hypertensive, Hyperinsulinemic, Hyperlipidemic Rats

et al. 2008

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“…Recently, it was reported that the Angiotensin-II receptor blocker (ARB) telmisartan [6][7][8][9][10][11][12][13][14][15][16][17] and sulfonylurea glimepiride act as ligands of PPARg 18,19 and their clinical usefulness in this context has received some attention, although characterization of these new PPARg ligands has not been fully clarified. Crystal structure of PPARg binding domains revealed a large binding pocket, which may explain the diversity of PPARg ligands.…”

Section: Introductionmentioning

confidence: 99%

“…20,21 Indeed, some studies showed that telmisartan bound to different sites of PPARg from TZDs, and recruited coactivators/corepressors in different manner from TZDs. [6][7][8]20 Although the characterization of glimepiride has not been clearly determined, glimepiride has been reported to have extra pancreatic effects or actions of improving insulin sensitivity as well as stimulatory effect on islet beta-cells. 22,23 The extrapancreatic effects of glimepiride would be partly originated from activation of PPARg.…”

Section: Introductionmentioning

confidence: 99%