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 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.

• Authors: Romain Harmancey, Truong N Lam, Genna M Lubrano, Patrick H Guthrie, Deborah Vela, Heinrich Taegtmeyer
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 26 Issue 8 Pg. 3118-26 (Aug 2012) ISSN: 1530-6860 [Electronic] United States
• PMID: 22611083 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Sucrose
• Insulin
• Ion Channels
• Mitochondrial Proteins
• Ucp3 protein, rat
• Uncoupling Protein 3
• Oleic Acid
• Glucose

Topics

• Animals
• Dietary Sucrose (administration & dosage, pharmacology)
• Down-Regulation
• Glucose (metabolism)
• Heart (physiology)
• In Vitro Techniques
• Insulin (physiology)
• Insulin Resistance (physiology)
• Ion Channels (metabolism)
• Mitochondrial Proteins (metabolism)
• Myocardial Contraction (drug effects)
• Myocardium (metabolism)
• Oleic Acid (metabolism)
• Perfusion
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Stress, Physiological (physiology)
• Uncoupling Protein 3