Diabetes mellitus — metabolic preconditioning in protecting the heart from ischemic damage?

Abstract

The negative impact of diabetes mellitus (DM) on the cardiovascular system has been confirmed by numerous clinical studies. However, there are experimental studies that show an increase in the resistance of the heart to ischemic and reperfusion damage in animals with DM. This phenomenon is characterized by a smaller size of the infarct zone, better preservation of the contractile function of the myocardium, and a lower incidence of ischemic and reperfusion arrhythmias. It is assumed that at a certain stage in the development of DM, a “metabolic window” is formed, in which metabolic alterations at the cellular level trigger adaptive mechanisms that increase the viability of cardiomyocytes. Published data confirm that the magnitude of the protective effect induced by DM is comparable to, and in some cases even exceeds, the effect of the preconditioning phenomenon. It is recognized that the mechanisms that protect the heart from ischemic and reperfusion damage against the background of DM are universal and are associated with the modulation of the antioxidant system, apoptosis factors, pro-inflammatory cytokines, and signaling systems that ensure cell survival. The one of the main pathogenic factor in DM is hyperglycemia, but under stress it plays the role of an adaptive mechanism aimed at meeting the increased energy demand in pathological conditions. Probably, at a certain stage of DM, hyperglycemia becomes a trigger for the development of protective effects and activates not only signaling pathways, but also the restructuring of energy metabolism, which makes it possible to maintain ATP production at a sufficient level to maintain the vital activity of heart cells under ischemia/reperfusion conditions. It is possible that an increased level of glucose, accompanied by the activation of insulin-independent mechanisms of its entry into cells, as well as the availability of this energy substrate, will contribute to a better restoration of energy production in heart cells after a infarction, which, in turn, will significantly reduce the degree of myocardial damage and will help preserve the contractile function of the heart. Identification of the conditions and mechanisms of the cardioprotective phenomenon induced by DM will make it possible to simulate the metabolic state in which the protection of cardiomyocytes from damaging factors is realized.

Keywords

• diabetes mellitus
• cardioprotection
• metabolic preconditioning, ischemic and reperfusion injury
• hyperglycemia, energy metabolism