Olmesartan Medoxomil, an Angiotensin II Receptor Blocker Ameliorates Insulin Resistance and Decreases Triglyceride Production in Fructose-Fed Rats

Okada, Kenta; Hirano, Tsutomu; Ran, Jianmin; Adachi, Mitsuru

doi:10.1291/hypres.27.293

Cited by 57 publications

(45 citation statements)

References 35 publications

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“…Therefore, the AT1 receptor blockade ameliorates these effects and partially explains the beneficial effects of telmisartan on fructoseinduced insulin resistance. Similar to our findings with telmisartan, a few other studies have shown favorable metabolic effects of other ARBs in fructose-fed rats (27)(28)(29). Collec- …”

Section: Discussionsupporting

confidence: 92%

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: Discussionsupporting

confidence: 92%

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

et al. 2008

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“…In addition, it improved glucose sensitivity. These data confirmed previous observations in humans and experimental animals without renal disease that showed that RAS blockers are able to ameliorate the metabolic adverse effects that are observed in MS (33)(34)(35)(36)(37)(38). However, to our knowledge, this is the first study to analyze the effect of ARB on IR that is associated with kidney disease.…”

Section: Discussionsupporting

confidence: 90%

Insulin Resistance, Inflammatory Biomarkers, and Adipokines in Patients with Chronic Kidney Disease

Vinuesa

Goicoechea

Kanter

et al. 2006

Journal of the American Society of Nephrology

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Patients with chronic kidney disease (CKD) present a high prevalence of insulin resistance (IR). Some studies suggest that angiotensin II may influence some cellular pathways that contribute to the pathogenesis of IR and stimulate the release of proinflammatory cytokines. Fifty-two patients who had stages 3 and 4 CKD and no diabetes were administered an angiotensin receptor blocker (ARB), olmesartan (40 mg), for 16 wk. Before and after ARB treatment, metabolic and inflammatory parameters and adipokines were measured. IR was calculated by Homeostasis Model Assessment (HOMA) index. Baseline data were compared with data that were obtained from 25 healthy control individuals of similar age and normal renal function. Compared with control subjects, patients with CKD presented significantly higher BP and waist circumference, higher triglycerides and lower HDL levels, higher insulin levels, and higher mean HOMA index (6.0 ؎ 2.7 versus 2.9 ؎ 2.2 U/ml ؋ mmol/L; P < 0.001). In addition, patients with CKD had increased levels of high-sensitivity C-reactive protein, TNF-␣, and IL-6. In patients with CKD, leptin was positively correlated to abdominal obesity, insulin levels, and IL-6, and adiponectin was inversely correlated to abdominal obesity and insulin levels. Olmesartan treatment resulted in a significant decrease of BP, urinary protein excretion, plasma glucose (99 ؎ 16 versus 92 ؎ 14 mg/dl; P < 0.05), insulin (23.1 ؎ 8.8 versus 19.9 ؎ 9; P < 0.05), HOMA index (6.0 ؎ 2.7 versus 4.7 ؎ 2.8; P < 0.05), and glycated hemoglobin (5.33 ؎ 0.58 versus 4.85 ؎ 0.81%; P < 0.01). At the same time, there was a significant reduction of high-sensitivity C-reactive protein levels, from 4.45 mg/L (2.45 to 9.00) to 3.55 mg/L (1.80 to 5.40; P < 0.05) and fibrinogen (412 ؎ 100 versus 370 ؎ 105 mg/dl; P < 0.05). There were no significant differences in adipokine levels after olmesartan treatment. These data demonstrate that patients with CKD have a high prevalence of IR, metabolic syndrome, and chronic inflammation and that the administration of the ARB olmesartan improves IR and inflammation markers in these patients. Plasma adipokine levels that are related to several metabolic risk factors in patients with CKD were not modified by ARB therapy.

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“…Daisuke KADOWAKI 1) , Makoto ANRAKU 1) , Yuka TASAKI 1) , Kenichiro KITAMURA 2) , Shiho WAKAMATSU 2) , Kimio TOMITA 2) , Janusz M. GEBICKI 3) , Toru MARUYAMA 1) , and Masaki OTAGIRI 1)…”

Section: Effect Of Olmesartan On Oxidative Stress In Hemodialysis Patunclassified

“…Angiotensin II type 1 (AT1) receptor blockers (ARBs) inhibit the RAAS and have been shown to be effective for treating hypertension (1,2). Independent of their ability to lower BP, these compounds have also been reported to reduce the progression of nephropathy in patients with diabetes mellitus (DM) and chronic kidney disease (CKD) (3)(4)(5). Although much of the renal protective effects of ARBs might be due to the lowering of BP, some protection may be due to their effects in reducing oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Effect of Olmesartan on Oxidative Stress in Hemodialysis Patients

et al. 2007

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Olmesartan Medoxomil, an Angiotensin II Receptor Blocker Ameliorates Insulin Resistance and Decreases Triglyceride Production in Fructose-Fed Rats

Cited by 57 publications

References 35 publications

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

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

Insulin Resistance, Inflammatory Biomarkers, and Adipokines in Patients with Chronic Kidney Disease

Effect of Olmesartan on Oxidative Stress in Hemodialysis Patients

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