Arterial insulin resistance in Yucatan micropigs with diet-induced obesity and metabolic syndrome.

Autor: Low Wang CC; Endocrine Section, VA Medical Center, Denver, and University of Colorado Anschutz Medical Campus/School of Medicine, Aurora, CO, USA. Cecilia.Wang@UCDenver.edu, Lu L, Leitner JW, Sarraf M, Gianani R, Draznin B, Greyson CR, Reusch JE, Schwartz GG
Jazyk: angličtina
Zdroj: Journal of diabetes and its complications [J Diabetes Complications] 2013 Jul-Aug; Vol. 27 (4), pp. 307-15. Date of Electronic Publication: 2013 Apr 02.
DOI: 10.1016/j.jdiacomp.2013.02.009
Abstrakt: Aim: Metabolic syndrome affects a large proportion of the population and increases cardiovascular disease risk. Because metabolic syndrome often co-exists clinically with atherosclerosis, it is difficult to distinguish the respective contributions of the components to vascular abnormalities. Accordingly, we utilized a porcine dietary model of metabolic syndrome without atherosclerosis to investigate early abnormalities of vascular function and signaling.
Methods: Thirty-two Yucatan micropigs were fed either a high-fat, high-simple-sugar, high-calorie (HFHS) or standard chow diet (STD) for 6 months. Neither diet contained added cholesterol. Blood pressure and flow-mediated vasodilatation were assessed at baseline and 6 months. Aortas were harvested at 6 months to assess histology, insulin signaling, and endothelial nitric oxide (eNOS) phosphorylation.
Results: HFHS pigs developed characteristics of metabolic syndrome including obesity, dyslipidemia, and insulin resistance, but without histologic evidence of atherosclerosis. Although arterial intima-media thickness did not differ between groups, vascular dysfunction in HFHS was manifest by increased blood pressure and impaired flow-mediated vasodilation of the femoral artery. Compared with STD, aortas from HFHS exhibited increased p85α expression and Ser307 IRS-1 phosphorylation, and blunted insulin-stimulated IRS-1-associated phosphatidylinositol (PI) 3-kinase activity. In the absence of insulin stimulation, aortic Akt Ser473-phosphorylation was greater in HFHS than in STD. With insulin stimulation, Akt phosphorylation increased in STD, but not HFHS. Insulin-induced Ser1177-phosphorylation of eNOS was decreased in HFHS, compared with STD.
Conclusions: Pigs with metabolic syndrome develop early vascular dysfunction and aortic insulin signaling abnormalities, and could be a useful model for early human vascular abnormalities in this condition.
(Copyright © 2013 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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