Open Access2型糖尿病的亚裔印度人中, 底物介导的心肌线粒体复合体I呼吸受损时脂肪酸代谢和氧化应激状态调节不变
Author(s) -
Jayakumari Nandini R.,
Rajendran Raji S.,
Sivasailam Ashok,
Vimala Surabhi S.,
Nanda Saurabh,
Manjunatha Shankarappa,
Pillai Vivek V.,
Karunakaran Jayakumar,
Gopala Srinivas
Publication year - 2020
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.13031
Subject(s) - mitochondrion , medicine , endocrinology , population , diabetes mellitus , fatty acid , oxidative phosphorylation , beta oxidation , respiration , fatty acid metabolism , mitochondrial dna , type 2 diabetes , carbohydrate metabolism , oxidative stress , metabolism , cellular respiration , biology , biochemistry , gene , anatomy , environmental health
Abstract Background 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 fibers and isolated mitochondria are metabolically compromised in the Caucasian population, studies of Asian Indian myocardial mitochondrial function are lacking. Thus, the objective of the present study is to analyze if there is altered cardiac mitochondrial substrate utilization in diabetic Asian Indians. Methods Mitochondrial substrate utilization was measured using high‐resolution respirometry in isolated mitochondria prepared from right atrial appendage tissues of diabetic and nondiabetic 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. Results The mitochondrial oxygen consumption rate for fatty acid substrate was shown to be decreased in diabetic subjects compared to nondiabetic subjects along with an 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. Conclusion 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 nondiabetic myocardium. Altered glutamate‐mediated mitochondrial respiration also points toward 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.