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Pyruvate Dehydrogenase Complex and Glucose Oxidation as a Therapeutic Target in Diabetic Heart Disease

Tabatabaei Dakhili Seyed Amirhossein|Amanda A. Greenwell|John R. Ussher
한국지질동맥경화학회 (The Korean Society of Lipidology and Atherosclerosis)|2023.01|지질·동맥경화학회지 (Journal of Lipid and Atherosclerosis)|제12권 제1호|pp. 47-57|DOI 10.12997/jla.2023.12.1.47

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키워드

Glucose oxidationDiastolic dysfunctionDiabetic cardiomyopathiesDiabetic heart diseaseCardiac energeticsPyruvate dehydrogenase

초록

Diabetic cardiomyopathy was originally described as the presence of ventricular dysfunction in the absence of coronary artery disease and/or hypertension. It is characterized by diastolic dysfunction and is more prevalent in people with diabetes than originally realized, leading to the suggestion in the field that it simply be referred to as diabetic heart disease. While there are currently no approved therapies for diabetic heart disease, a multitude of studies clearly demonstrate that it is characterized by several disturbances in myocardial energy metabolism. One of the most prominent changes in myocardial energy metabolism in diabetes is a robust impairment in glucose oxidation. Herein we will describe the mechanisms responsible for the diabetes-induced decline in myocardial glucose oxidation, and the pharmacological approaches that have been pursued to correct this metabolic disorder. With surmounting evidence that stimulating myocardial glucose oxidation can alleviate diastolic dysfunction and other pathologies associated with diabetic heart disease, this may also represent a novel strategy for decreasing the prevalence of heart failure with preserved ejection fraction in the diabetic population.

Abstract

Diabetic cardiomyopathy was originally described as the presence of ventricular dysfunction in the absence of coronary artery disease and/or hypertension. It is characterized by diastolic dysfunction and is more prevalent in people with diabetes than originally realized, leading to the suggestion in the field that it simply be referred to as diabetic heart disease. While there are currently no approved therapies for diabetic heart disease, a multitude of studies clearly demonstrate that it is characterized by several disturbances in myocardial energy metabolism. One of the most prominent changes in myocardial energy metabolism in diabetes is a robust impairment in glucose oxidation. Herein we will describe the mechanisms responsible for the diabetes-induced decline in myocardial glucose oxidation, and the pharmacological approaches that have been pursued to correct this metabolic disorder. With surmounting evidence that stimulating myocardial glucose oxidation can alleviate diastolic dysfunction and other pathologies associated with diabetic heart disease, this may also represent a novel strategy for decreasing the prevalence of heart failure with preserved ejection fraction in the diabetic population.

참고문헌 (53)

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