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FASEB J. 2012 Aug;26(8):3118-26. doi: 10.1096/fj.12-208991. Epub 2012 May 18.

Insulin resistance improves metabolic and contractile efficiency in stressed rat heart.

Author information

1
Department of Internal Medicine, Division of Cardiology, University of Texas Medical School at Houston, Houston, Texas 77030, USA. heinrich.taegtmeyer@uth.tmc.edu

Abstract

Insulin resistance is a prominent feature in heart failure, while hyperglycemia impairs cardiac contraction. We propose that decreased insulin-mediated glucose uptake by the heart preserves cardiac function in response to metabolic and hemodynamic stress. To test this hypothesis, we fed rats a high-sucrose diet (HSD). Energy substrate metabolism and cardiac work were determined ex vivo in a sequential protocol simulating metabolic and hemodynamic stress. Compared to chow-fed, control rats, HSD impaired myocardial insulin responsiveness and induced profound metabolic changes in the heart, characterized by reduced rates of glucose uptake (7.91 ± 0.30 vs. 10.73 ± 0.67 μmol/min/g dry weight; P<0.001) but increased rates of glucose oxidation (2.38 ± 0.17 vs. 1.50 ± 0.15 μmol/min/g dry weight; P<0.001) and oleate oxidation (2.29 ± 0.11 vs. 1.96 ± 0.12 μmol/min/g dry weight; P<0.05). Tight coupling of glucose uptake and oxidation and improved cardiac efficiency were associated with a reduction in glucose 6-phosphate and oleoyl-CoA levels, as well as a reduction in the content of uncoupling protein 3. Our results suggest that insulin resistance lessens fuel toxicity in the stressed heart. This calls for a new exploration of the mechanisms regulating substrate uptake and oxidation in the insulin-resistant heart.

PMID:
22611083
PMCID:
PMC3405268
DOI:
10.1096/fj.12-208991
[Indexed for MEDLINE]
Free PMC Article

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