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Effect of metformin on vascular alterations promoted by aortic perivascular adipose tissue of obese rats: role of AMP-activated kinase (AMPK)

Grant number: 11/06303-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2011
Effective date (End): June 30, 2012
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal researcher:Eliana Hiromi Akamine
Grantee:Paula Kimie Honda
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Recent studies have shown that fat accumulation in the perivascular region may be involved with vascular dysfunction in obesity, in the same way as visceral fat. The AMP-activated kinase (AMPK) is an enzyme that participates of energy homeostasis and also regulates the vascular function, for example by increasing the endothelial nitric oxide synthase (eNOS) phosphorylation. Perivascular adipose tissue reduces expression of AMPK in aorta from obese rats. AMPK mediates, at least in part, the effects of metformin, which is the most used drug for the treatment of type 2 diabetes. Thus, the hypothesis of the present study is that metformin could correct the vascular dysfunction, by promoting direct effects on perivascular adipose tissue, which in the end activate the AMPK/eNOS pathway. The aim of the present project, therefore, will be to evaluate the effects of metformin on the regulation of aortic reactivity by perivascular adipose tissue in obese rats, emphasizing the AMPK/eNOS pathway. To achieve this objective, we will evaluate the vasoconstrictor response to noradrenaline, the endothelium-dependent relaxation to acetylcholine, and the endothelium-independent relaxation to sodium nitroprusside in the aorta of monosodium glutamate-induced obese rats, with or freed of perivascular adipose tissue, treated or not with metformin. The vascular reactivity will also be studied in the presence of compound C, an AMPK inhibitor, to evaluate its participation in the effect of metformin. We will also evaluate the total and phosphorylated expression of AMPK and eNOS in aorta with or freed of perivascular adipose tissue of obese rats treated with metformin. We anticipate that this study will contribute to understand the role of AMPK in the vascular effects of metformin.

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