Diabetic alterations of myocardial metabolism are stimulated mainly by malfunctions of acetyl-coenzyme-A-carboxylase, carnitine-palmitoyl-transferase-I and pyruvate-dehydrogenase inducing an overshoot of fatty acid oxidation which inhibits glucose oxidation. Gene expression of pyruvate-dehydrogenase and glucose transporters as well as depression of the third step of mitochondrial respiratory chain contribute also to the diabetic alterations of myocardial metabolism. Ischaemic cardiovascular alterations are frequent and their treatment is not so successful in diabetes. Its reason lies in the fact that fatty acid oxidation is the costliest oxygen metabolic pathway. Therefore, aerobic glycolysis gradually shifts to anaerobic one under ischaemia in diabetes, and accumulates lactate and acid metabolites inducing myocardial deteriorations. Animal experiments demonstrate that elective depression of carinite-palmitoyltransferase-I enzyme-activity promotes glucose oxidation and the early rapid recovery of myocardial contractility especially under diabetic conditions. Trimetazidine optimizes energy metabolism by reducing oxygen demand without reducing energy supply and altering heart activity blocking fatty-3-ketoacyl-CoA-thiolase enzyme of beta-oxidation and inhibiting the overshoot of fatty oxidation. Trimetazidine has, therefore, a permanent myocardial cytoprotection in stable angina pectoris. However, its beneficial antianginal effect could be observed only under good controlled conditions according our observation.
|Translated title of the contribution||Energy metabolism in diabetics - Therapeutic implications|
|Number of pages||6|
|Publication status||Published - Dec 1 2001|
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