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


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 ?mol/min/g dry weight; P<0.001) but increased rates of glucose oxidation (2.38 ± 0.17 vs. 1.50 ± 0.15 ?mol/min/g dry weight; P<0.001) and oleate oxidation (2.29 ± 0.11 vs. 1.96 ± 0.12 ?mol/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.

SUBMITTER: Harmancey R 

PROVIDER: S-EPMC3405268 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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

Harmancey Romain R   Lam Truong N TN   Lubrano Genna M GM   Guthrie Patrick H PH   Vela Deborah D   Taegtmeyer Heinrich H  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20120518 8


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 i  ...[more]

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