Affiliation:
1. Department of Medical Physiology, University of Tromsø, N-9037 Tromsø, Norway;
2. Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada T2N 4N1; and
3. Department of Cardiology and Medicine, University of Edinburgh, Edinburgh EH8 9XF, Scotland
Abstract
Hearts from diabetic db/ db mice, a model of Type 2 diabetes, exhibit left ventricular failure and altered metabolism of exogenous substrates. Peroxisome proliferator-activated receptor-α (PPAR-α) ligands reduce plasma lipid and glucose concentrations and improve insulin sensitivity in db/ db mice. Consequently, the effect of 4- to 5-wk treatment of db/ db mice with a novel PPAR-α ligand (BM 17.0744; 25–38 mg · kg−1 · day−1), commencing at 8 wk of age, on ex vivo cardiac function and metabolism was determined. Elevated plasma concentrations of glucose, fatty acids, and triacylglycerol (34.0 ± 3.6, 2.0 ± 0.4, and 0.9 ± 0.1 mM, respectively) were reduced to normal after treatment with BM 17.0744 (10.8 ± 0.6, 1.1 ± 0.1, and 0.6 ± 0.1 mM). Plasma insulin was also reduced significantly in treated compared with untreated db/ db mice. Chronic treatment of db/ db mice with the PPAR-α agonist resulted in a 50% reduction in rates of fatty acid oxidation, with a concomitant increase in glycolysis (1.7-fold) and glucose oxidation (2.3- fold). Correction of the diabetes-induced abnormalities in systemic and cardiac metabolism after BM 17.0744 treatment did not, however, improve left ventricular contractile function.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
138 articles.
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