Autophagic predisposition in the insulin resistant diabetic heart

Existence of a diabetic cardiopathology, independent of vascular abnormalities, has been well reported. Diffuse interstitial fibrosis throughout the diabetic myocardium (even in the absence of an acute coronary event) suggests widespread cardiomyocyte attrition and cytokine activity. In addition to apoptotic and necrotic events, there is now good evidence that significant cardiomyocyte loss in the diabetic heart is driven by a different, non-apoptotic type of programmed cell death: autophagy. Although considered to be beneficial and pro-survival as a short term strategy to deal with acute stress, when chronically elevated or constitutive, excess autophagic activity has potential to be lethal. The insulin resistant myocardium exhibits various pro-autophagic characteristics: suppression of the PI3K(I)-Akt signaling pathway, oxidative stress and metabolic dysregulation, rendering the diabetic heart vulnerable to autophagic demise. There is compelling new evidence that in the diabetic myocardium cardiomyocyte attrition can be linked to autophagic upregulation.

Autophagy signaling pathway schematic depicting involvement of PI3K(I)-Akt and AMPK signaling, potential upstream mediators of autophagy induction in diabetes.Figure optionsDownload high-quality image (153 K)Download as PowerPoint slide