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Improvement of metabolic parameters and vascular function by metformin in obese non-diabetic rats.

Abstract：

AIMS:Metformin is an insulin sensitizing agent with beneficial effects in diabetic patients on glycemic levels and in the cardiovascular system. We examined whether the metabolic changes and the vascular dysfunction in monosodium glutamate-induced obese non-diabetic (MSG) rats might be improved by metformin. MAIN METHODS:16 week-old MSG rats were treated with metformin for 15 days and compared with age-matched untreated MSG and non-obese non-diabetic rats (control). Blood pressure, insulin sensitivity, vascular reactivity and prostanoid release in the perfused mesenteric arteriolar bed as well as nitric oxide production and reactive oxygen species generation in isolated mesenteric arteries were analyzed. KEY FINDINGS:18-week-old MSG rats displayed higher Lee index, fat accumulation, dyslipidemia, insulin resistance and hyperinsulinemia. Metformin treatment improved these alterations. The norepinephrine-induced response, increased in the mesenteric arteriolar bed from MSG rats, was corrected by metformin. Indomethacin corrected the enhanced contractile response in MSG rats but did not affect metformin effects. The sensitivity to acetylcholine, reduced in MSG rats, was also corrected by metformin. Indomethacin corrected the reduced sensitivity to acetylcholine in MSG rats but did not affect metformin effects. The sensitivity to sodium nitroprusside was increased in preparations from metformin-treated rats. Metformin treatment restored both the reduced PGI2/TXA2 ratio and the increased reactive oxygen species generation in preparations from MSG rats. SIGNIFICANCE:Metformin improved the vascular function in MSG rats through reduction in reactive oxygen species generation, modulation of membrane hyperpolarization, correction of the unbalanced prostanoids release and increase in the sensitivity of the smooth muscle to nitric oxide.

journal_name

Life Sci

journal_title

Life sciences

authors

Lobato NS,Filgueira FP,Hagihara GN,Akamine EH,Pariz JR,Tostes RC,Carvalho MH,Fortes ZB

doi

10.1016/j.lfs.2011.11.005

subject

Has Abstract

pub_date

2012-01-30 00:00:00

pages

228-35

issue

5-6

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(11)00567-4

journal_volume

pub_type

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Improvement of metabolic parameters and vascular function by metformin in obese non-diabetic rats.