The Impact of Diabetes Mellitus on Oxygen Utilization by Complex IV: Preliminary Insights

Abstract

Background: The protein complexes of the electron transport chain have been linked to the pathogenesis of diabetes mellitus (DM), but the interplay between DM and cytochrome c oxidase (complex IV) is not well understood. In this study, using a rat DM model, we evaluated the effect of DM on liver and kidney mitochondria, looking specifically at the characteristics of oxygen consumption by complex IV; we also studied the effects of DM on the protein composition of liver and kidney mitochondria.

Cytochrome c Oxidase Activity as a Metabolic Regulator in Pancreatic Beta-Cells

“…More specifically, OxPhos genes were differentially expressed, and DNA methylation was found in these genes in islets from patients with T2D compared with nondiabetic donors [13,14]. Impairments in OxPhos activity [16,28,29] and differentially expressed OxPhos genes were found in islets from patients with T2D compared with nondiabetic donors [13,14] as well as in animal models of diabetes [15,41], supporting a pivotal role of the mitochondria OxPhos in β-cell dysfunc-tion. However, data regarding COX dysfunction and its role in pancreatic islets and β-cell function are limited.…”

“…An abnormal mitochondrial morphology and reduced GSIS have been found in β cells from postmortem T2D patients [8][9][10]. Impairments in OxPhos [16,28,29] and diminished mitochondrial activity have been demonstrated in diabetes patients [2,4,11,12,27,[30][31][32][33][34][35], while mutations in the mitochondrial genome such as the mtDNA 3243 mutation were shown to be associated with diabetes [36][37][38][39][40]. More specifically, OxPhos genes were differentially expressed, and DNA methylation was found in these genes in islets from patients with T2D compared with nondiabetic donors [13,14].…”