Metabolic abnormalities of the heart in type II diabetes.
Type 2 diabetes mellitus escalates the risk of heart failure partly via its ability to induce a cardiomyopathic state that is independent of coronary artery disease and hypertension. Although the pathogenesis of diabetic cardiomyopathy has yet to be fully elucidated, aberrations in cardiac substrate metabolism and energetics are thought to be key drivers. These aberrations include excessive fatty acid utilisation and storage, suppressed glucose oxidation and impaired mitochondrial oxidative phosphorylation. An appreciation of how these abnormalities arise and synergise to promote adverse cardiac remodelling is critical to their effective amelioration. This review focuses on disturbances in myocardial fuel (fatty acids and glucose) flux and energetics in type 2 diabetes, how these disturbances relate to the development of diabetic cardiomyopathy and the potential therapeutic agents that could be used to correct them.
British Heart Foundation Centre of Excellence, Cardiovascular Division, King's College London, London, UK.
Nelson
N
Amaral
British Heart Foundation Centre of Excellence, Cardiovascular Division, King's College London, London, UK obiokonko@aol.com.
Darlington O
DO
Okonko
D000975:Antioxidants / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010480:Perhexiline / Q000627:therapeutic use; D000069458:Ranolazine / Q000627:therapeutic use; D014292:Trimetazidine / Q000627:therapeutic use; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000627:therapeutic use
D000975:Antioxidants; D002317:Cardiovascular Agents; D005227:Fatty Acids; D009943:Organophosphorus Compounds; D014451:Ubiquinone; C429014:mitoquinone; D000069458:Ranolazine; D005947:Glucose; D010480:Perhexiline; D014292:Trimetazidine
Metabolism; diabetes; energetics