Altered mitochondrial metabolism in the insulin-resistant heart


Makrecka-Kuka M., Liepinsh E., Murray A. J., Lemieux H., Dambrova M., Tepp K., ...More

Acta Physiologica, vol.228, no.3, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 228 Issue: 3
  • Publication Date: 2020
  • Doi Number: 10.1111/apha.13430
  • Journal Name: Acta Physiologica
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, SportDiscus, Veterinary Science Database
  • Keywords: diabetes, heart, lipotoxicity, mitochondria, FATTY-ACID OXIDATION, MYOCARDIAL SUBSTRATE METABOLISM, CARDIOVASCULAR RISK-FACTORS, MALONYL-COA DECARBOXYLASE, FREE-RADICAL GENERATION, NITRIC-OXIDE, DIABETIC CARDIOMYOPATHY, RESPIRATORY-CHAIN, ENERGY-METABOLISM, UNCOUPLING PROTEIN-3
  • Lokman Hekim University Affiliated: No

Abstract

© 2019 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological SocietyObesity-induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA-induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.