The Mitochondria: A Target of Polyphenols in the Treatment of Diabetic Cardiomyopathy

Abstract

Diabetic cardiomyopathy (DCM) is a constellation of symptoms consisting of ventricular dysfunction and cardiomyocyte disarray in the presence of diabetes. The exact cause of this type of cardiomyopathy is still unknown; however, several processes involving the mitochondria, such as lipid and glucose metabolism, reactive oxygen species (ROS) production, apoptosis, autophagy and mitochondrial biogenesis have been implicated. In addition, polyphenols have been shown to improve the progression of diabetes. In this review, we discuss some of the mechanisms by which polyphenols, particularly resveratrol, play a role in slowing the progression of DCM. The most important intermediates by which polyphenols exert their protective effect include Bcl-2, UCP2, SIRT-1, AMPK and JNK1. Bcl-2 acts to attenuate apoptosis, UCP2 decreases oxidative stress, SIRT-1 increases mitochondrial biogenesis and decreases oxidative stress, AMPK increases autophagy, and JNK1 decreases apoptosis and increases autophagy. Our dissection of these molecular players aims to provide potential therapeutic targets for the treatment of DCM.

Keywords: autophagy; diabetic cardiomyopathy; polyphenols; resveratrol.

Figure 1

Summary of the effect of resveratrol on the mitochondrial reactive oxygen species (ROS) generation and apoptosis pathways. Resveratrol action is primarily mediated through UCP2 and Bcl-2. Diallyl trisulfide (DATS) is another polyphenol derived from garlic, which mediates its anti-apoptotic effect through Nrf2.

Figure 2

Summary of the effects of resveratrol on mitochondrial biogenesis, oxidative stress and lipid accumulation, all of which are mediated by SIRT1.

Figure 3

Summary of the effects of resveratrol on autophagy and apoptosis, mediated primarily by JNK1 and AMPK.