Cardiac Insulin Resistance in Heart Failure: The Role of Mitochondrial Dynamics

Abstract

Heart failure (HF) frequently coexists with conditions associated with glucose insufficiency, such as insulin resistance and type 2 diabetes mellitus (T2DM), and patients with T2DM have a significantly high incidence of HF. These two closely related diseases cannot be separated on the basis of their treatment. Some antidiabetic drugs failed to improve cardiac outcomes in T2DM patients, despite lowering glucose levels sufficiently. This may be, at least in part, due to a lack of understanding of cardiac insulin resistance. Basic investigations have revealed the significant contribution of cardiac insulin resistance to the pathogenesis and progression of HF; however, there is no clinical evidence of the definition or treatment of cardiac insulin resistance. Mitochondrial dynamics play an important role in cardiac insulin resistance and HF because they maintain cellular homeostasis through energy production, cell survival, and cell proliferation. The innovation of diagnostic tools and/or treatment targeting mitochondrial dynamics is assumed to improve not only the insulin sensitivity of the myocardium and cardiac metabolism, but also the cardiac contraction function. In this review, we summarized the current knowledge on the correlation between cardiac insulin resistance and progression of HF, and discussed the role of mitochondrial dynamics on the pathogenesis of cardiac insulin resistance and HF. We further discuss the possibility of mitochondria-targeted intervention to improve cardiac metabolism and HF.

Energy metabolism disorders and potential therapeutic drugs in heart failure

“…In fact, glucose metabolism and fatty acid metabolism in the heart are strictly controlled by insulin signal. Impaired insulin signal or insulin resistance play a decisive role in the occurrence and development of HF 96 . Therefore, the correction of insulin resistance and the elimination of insulin signal-mediated interference factors in patients with HF are of positive significance to prevent heart disease and improve the prognosis of patients with HF.…”

Advances in Cardiotoxicity Induced by Altered Mitochondrial Dynamics and Mitophagy

“…Past studies have established that hunger or reduced insulin signals are a strong trigger for autophagy ( 92 , 184 , 185 ). Hyperglycemia can induce myocardial mitochondria division but inhibit mitophagy, causing the accumulation of functionally impaired mitochondria ( 57 , 186 , 187 ). Additionally, DRP1 and ROS have mutually reinforcing associations ( 188 ).…”

Marine-Derived Omega-3 Polyunsaturated Fatty Acids and Heart Failure: Current Understanding for Basic to Clinical Relevance

“…Alteration of energetic substrate utilization in myocardium and modification of its intra-cellular signaling pathway also play important roles for the pathogenesis and progression of HF [81]. Previous animal studies revealed that the dietary n-3 PUFA intake altered the mitochondrial membrane phospholipid composition in cardiomyocytes, which led to a decrease in myocardial oxygen consumption without loss of ventricular power generation [82,83].…”