title: Impaired Mitochondrial Respiration in Large Cerebral Arteries of Rats with Type 2 Diabetes.
abstract: Mitochondrial dysfunction has been suggested as a potential underlying cause of pathological conditions associated with type 2 diabetes (T2DM). We have previously shown that mitochondrial respiration and mitochondrial protein levels were similar in the large cerebral arteries of insulin-resistant Zucker obese rats and their lean controls. In this study, we extend our investigations into the mitochondrial dynamics of the cerebral vasculature of 14-week-old Zucker diabetic fatty obese (ZDFO) rats with early T2DM. Body weight and blood glucose levels were significantly higher in the ZDFO group, and basal mitochondrial respiration and proton leak were significantly decreased in the large cerebral arteries of the ZDFO rats compared with the lean controls (ZDFL). The expression of the mitochondrial proteins total manganese superoxide dismutase (MnSOD) and voltage-dependent anion channel (VDAC) were significantly lower in the cerebral microvessels, and acetylated MnSOD levels were significantly reduced in the large arteries of the ZDFO group. Additionally, superoxide production was significantly increased in the microvessels of the ZDFO group. Despite evidence of increased oxidative stress in ZDFO, exogenous SOD was not able to restore mitochondrial respiration in the ZDFO rats. Our results show, for the first time, that mitochondrial respiration and protein levels are compromised during the early stages of T2DM.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Merdzo
authors.forename: Ibolya
authors.initials: I
authors.lastname: Rutkai
authors.forename: Venkata N L R
authors.initials: VN
authors.lastname: Sure
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McNulty
authors.forename: Prasad V G
authors.initials: PV
authors.lastname: Katakam
authors.forename: David W
authors.initials: DW
authors.lastname: Busija
mesh_terms: D000107:Acetylation; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D019069:Cell Respiration; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism*; D002561:Cerebrovascular Disorders / Q000209:etiology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D055806:Microvessels / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000187:drug effects; D018384:Oxidative Stress; D011924:Rats, Zucker; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D016166:Free Radical Scavengers; D050994:Voltage-Dependent Anion Channels; D013481:Superoxides; D013482:Superoxide Dismutase