Journal article
Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts
Diabetes (New York, N.Y.), Vol.53(9), pp.2366-2374
2004
DOI: 10.2337/diabetes.53.9.2366
PMID: 15331547
Abstract
Diabetes alters cardiac substrate metabolism. The cardiac phenotype in insulin-resistant states has not been comprehensively characterized. The goal of these studies was to determine whether the hearts of leptin-deficient 8-week-old ob/ob mice were able to modulate cardiac substrate utilization in response to insulin or to changes in fatty acid delivery. Ob/ob mice were insulin resistant and glucose intolerant. Insulin signal transduction and insulin-stimulated glucose uptake were markedly impaired in ob/ob cardiomyocytes. Insulin-stimulated rates of glycolysis and glucose oxidation were 1.5- and 1.8-fold higher in wild-type hearts, respectively, versus ob/ob, and glucose metabolism in ob/ob hearts was unresponsive to insulin. Increasing concentrations of palmitate from 0.4 mmol/l (low) to 1.2 mmol/l (high) led to a decline in glucose oxidation in wild-type hearts, whereas glucose oxidation remained depressed and did not change in ob/ob mouse hearts. In contrast, fatty acid utilization in ob/ob hearts was 1.5- to 2-fold greater in the absence or presence of 1 nmol/l insulin and rose with increasing palmitate concentrations. Moreover, the ability of insulin to reduce palmitate oxidation rates was blunted in the hearts of ob/ob mice. Under low-palmitate and insulin-free conditions, cardiac performance was significantly greater in wild-type hearts. However, in the presence of high palmitate and 1 nmol/l insulin, cardiac performance in ob/ob mouse hearts was relatively preserved, whereas function in wild-type mouse hearts declined substantially. Under all perfusion conditions, myocardial oxygen consumption was higher in ob/ob hearts, ranging from 30% higher in low-palmitate conditions to greater than twofold higher under high-palmitate conditions. These data indicate that although the hearts of glucose-intolerant ob/ob mice are capable of maintaining their function under conditions of increased fatty acid supply and hyperinsulinemia, they are insulin-resistant, metabolically inefficient, and unable to modulate substrate utilization in response to changes in insulin and fatty acid supply.
Details
- Title: Subtitle
- Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts
- Creators
- Pradip K MAZUMDER - Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, The University of Utah School of Medicine, Salt Lake City, Utah, United StatesBrian T O'NEILL - Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, The University of Utah School of Medicine, Salt Lake City, Utah, United StatesMatthew W ROBERTS - Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, The University of Utah School of Medicine, Salt Lake City, Utah, United StatesJonathan BUCHANAN - Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, The University of Utah School of Medicine, Salt Lake City, Utah, United StatesUi Jeong Yun - Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, The University of Utah School of Medicine, Salt Lake City, Utah, United StatesRobert C COOKSEY - Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, The University of Utah School of Medicine, Salt Lake City, Utah, United StatesSihem BOUDINA - Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, The University of Utah School of Medicine, Salt Lake City, Utah, United StatesE. Dale ABEL - Program in Human Molecular Biology and Genetics, Division of Endocrinology, Metabolism and Diabetes, The University of Utah School of Medicine, Salt Lake City, Utah, United States
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.53(9), pp.2366-2374
- Publisher
- American Diabetes Association; Alexandria, VA
- DOI
- 10.2337/diabetes.53.9.2366
- PMID
- 15331547
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Language
- English
- Date published
- 2004
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025291402771
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