Diabetes-related metabolic perturbations in cardiac myocytePerturbations métaboliques des cardiomyocytes liées au diabète

https://doi.org/10.1016/S1262-3636(08)70096-XGet rights and content

Abstract

Although the pathogenesis of diabetic cardiomyopathy is poorly understood, recent evidence implicates perturbations in cardiac energy metabolism. Whereas mitochondrial fatty acid oxidation is the chief energy source for the normal postnatal mammalian heart, the relative contribution of glucose utilization pathways is significant, allowing the plasticity necessary for steady ATP production in the context of diverse physiologic and dietary conditions. In the uncontrolled diabetic state, because of the combined effects of insulin resistance and high circulating fatty acids, cardiac myocytes use fatty acids almost exclusively to support ATP synthesis. Studies using various diabetic rodent models have shown a direct relationship between the chronic drive on myocardial fatty acid metabolism and the development of cardiomyopathy including ventricular hypertrophy and dysfunction. Fatty acids also play a critical role in triggering the development of cellular insulin resistance through derangements in insulin signalling cascade. There are similarities in cardiac dysfunction in animal models and human type 2 diabetes and/or obesity. For instance, obese young women showed increased cardiac fatty acid utilization measured by positron emission tomography and increased myocardial oxygen consumption with reduced cardiac efficiency. Furthermore, accumulation of triglycerides within cardiac myocytes was an early metabolic marker that was associated with increased left ventricular mass. Moreover, data indicate that alterations in cardiac energetics occur early in the pathophysiology of type 2 diabetes and are correlated negatively with the fasting plasma free fatty acid concentrations.

Résumé

Nombre de données récentes, obtenues chez l’animal et chez l’homme, indiquent que le diabète est associé à des altérations du métabolisme énergétique des myocytes cardiaques. Bien que l’oxydation mitochondriale des acides gras à longue chaîne représente normalement la source principale d’énergie pour le myocarde, la contribution des voies d’utilisation intracellulaire du glucose est significative et elle permet, notamment, l’adaptabilité nécessaire de la production d’ATP aux diverses conditions physiologiques et nutritionnelles. Au cours du diabète, l’entrée des acides gras dans les myocytes cardiaques est majorée, d’une part en raison de leur plus grande disponibilité, et, d’autre part, de la réduction de l’utilisation du glucose qui accompagne l’insulino-résistance. L’oxydation très largement prédominante des acides gras est associée à une augmentation de consommation d’oxygène du myocarde et à une accumulation cellulaire de dérivés lipidiques. Les altérations métaboliques des cardiomyocytes au cours du diabète peuvent elles-mêmes être à l’origine d’anomalies de la structure (remodelage ventriculaire) et de la fonction ventriculaires cardiaques.

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