Metabolic and Contractile Remodelling in the Diabetic Heart: An Evolutionary Perspective

Abstract

The application of evolutionary biology to the study of human disease has given rise to the idea that disease can result from inappropriate adaptations to a change in environment. This concept can also be applied to the function of organs and responding to their local environments within the human body. The heart is an omnivorous organ which can use any substrate it is supplied with. The metabolic machinery of the heart is exquisitely attuned both to its metabolic needs and to the available energy substrates in its local environment. Diabetic cardiomyopathy is a disease process which arises as a result of the inability of the heart to adapt to a diabetic metabolic milieu. The heart becomes locked into a progressively maladaptive state from which it cannot escape by its own devices; due to the phenomenon of hyperglycemic memory, even restoration of a normal milieu may not be sufficient to completely reverse the remodeling. The pathways which initiate, progress and perpetuate this downward spiral are the same pathways which normally allow the heart to sense and respond to its local metabolic environment. These include metabolite-sensitive transcriptional regulatory pathways and, most probably, epigenetic and miRNA regulatory pathways. Overall, the application of evolutionary concepts provides a valuable framework for understanding the origins and importance of metabolic and contractile disturbances in the diabetic heart, and a strong rationale for the use of metabolic therapy as a treatment.