Disturbed Fatty Acid Oxidation, Endoplasmic Reticulum Stress, and Apoptosis in Left Ventricle of Patients With Type 2 Diabetes

Diabetes
Marko LjubkovicJasna Marinovic

Abstract

Chronic heart failure is a common complication in patients with type 2 diabetes mellitus (T2DM). T2DM is associated with disturbed metabolism of fat, which can result in excessive accumulation of lipids in cardiac muscle. In the current study, we assessed mitochondrial oxidation of carbohydrates and fatty acids, lipid accumulation, endoplasmic reticulum (ER) stress, and apoptosis in diabetic left ventricle. Left ventricular myocardium from 37 patients (a group of patients with diabetes and a group of patients without diabetes [ejection fraction >50%]) undergoing coronary artery bypass graft surgery was obtained by subepicardial needle biopsy. The group with diabetes had a significantly decreased rate of mitochondrial respiration fueled by palmitoyl-carnitine that correlated with blood glucose dysregulation, while there was no difference in oxidation of pyruvate. Diabetic myocardium also had significantly decreased activity of hydroxyacyl-CoA dehydrogenase (HADHA) and accumulated more lipid droplets and ceramide. Also, markers of ER stress response (GRP78 and CHOP) and apoptosis (cleaved caspase-3) were elevated in diabetic myocardium. These results show that, even in the absence of contractile failure, diabetic heart exhibits a...Continue Reading

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Citations

Dec 17, 2019·Acta Physiologica·Marina Makrecka-KukaTerje S Larsen
May 13, 2020·The Journal of Biological Chemistry·Jean E Schaffer
May 1, 2020·Frontiers in Cell and Developmental Biology·Yue JinYaoliang Tang
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Jun 1, 2021·Frontiers in Endocrinology·Haitao ZhangYaoliang Tang
Jul 20, 2021·Frontiers in Medicine·Teresa SalvatoreFerdinando Carlo Sasso
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Dec 11, 2021·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·An YanLiping Guo

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