Abstract
Objective: Glucagon-like peptide-1 analog and DPP4 inhibitors are reported to have cardio-protective properties against atherosclerosis and cardiac function in vitro and in vivo, however, concerns that incretin -related drug can increase the risk of heart failure also have been arisen. Therefore, the purpose of this study was to elucidate the effects and the mechanisms of incretin-related drugs on failing heart in vivo. Design and method: We used J2N-k hamsters which develop dilated cardiomyopathy and heart failure. Hamsters were randomized to receive PBS or GLP-1 analog (liraglutide) for 6 weeks using Alzet osmotic pumps. In the complementary experiments, J2N-k hamsters were treated 10% glucose as drinking solution. Results: In GLP-1 analog group, energy starvation and increased apoptosis in cardiac tissue were detected by up-regulated LC3 2/1 and cleaved caspase-3. Indirect calorimetry showed increased RQ value in failing heart and this dependency on carbohydrate augmented by administration of GLP-1 analog. In the complementary experiment, glucose was additionally supplied to GLP-1 analog-treated group. As a result, heart failure induced by GLP-1 analog were dramatically ameliorated by adequate glucose supply, exerting improved cardiac function and mortality, and marked the highest RQ value, suggesting heart muscle treated with incretin-related drug need much more carbohydrate as energy substrate to maintain cardiac function. Conclusions: Extra higher glucose-demand arose and cardiac function was exacerbated by treatment with incretin-related drug in failing heart, which was caused as the result that energy, especially glucose, could not meet the augmented carbohydrate demand by GLP-1 analog. Incretin-related treatment with an appropriate glycemic balance as energy regulation should be required when applying GLP-1 analogue to the patients with heart failure.
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