Jayakumari 2020 J Diabetes
|Jayakumari NR, Rajendran RS, Sivasailam A, Vimala SS, Nanda S, Manjunatha S, Pillai VV, Karunakaran J, Gopala S (2020) Impaired substrate-mediated cardiac mitochondrial complex I respiration with unaltered regulation of fatty acid metabolism and oxidative stress status in type 2 diabetic Asian Indians. J Diabetes 12:542-55.|
Abstract: The cardiovascular complications associated with type 2 diabetes mellitus could be attributed to changes in myocardial mitochondrial metabolism. Though it is a known fact that permeabilized cardiac muscle fibres as well as isolated mitochondria are metabolically compromised in Caucasian population, studies in Asian Indian myocardial mitochondrial function are lacking. Thus, the objective of the present study was to analyze if there is altered cardiac mitochondrial substrate utilization in diabetic Asian Indians.
Mitochondrial substrate utilization was measured using high-resolution respirometry in isolated mitochondria prepared from right atrial appendage tissues of diabetic and non-diabetic subjects undergoing coronary artery bypass graft surgery. Western blotting and densitometric analysis were also done to compare the levels of proteins involved in fatty acid metabolism and regulation.
Mitochondrial oxygen consumption rate for fatty acid substrate was shown to be decreased between diabetic and non-diabetic subjects along with unvaried mitochondrial DNA copy number and uniform levels of electron transport chain complex proteins and proteins involved in fatty acid metabolism and regulation. Decreased glutamate but unchanged pyruvate-mediated state 3 respiration were also observed in diabetic subjects.
The current study reports deranged cardiac mitochondrial fatty acid-mediated complex I respiration in type 2 diabetic Asian Indians with comparable levels of regulators of fatty acid oxidation to that of non-diabetic myocardium. Altered glutamate-mediated mitochondrial respiration also point towards possible alterations in mitochondrial complex I activity. When compared with previous reports on other ethnic populations, the current study suggests that Asian Indian population too have altered cardiac mitochondrial substrate utilization.
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Labels: MiParea: Respiration Pathology: Diabetes
Organism: Human Tissue;cell: Heart Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, S, NS, ROX HRR: Oxygraph-2k