Abstract 19124: Impaired Mitochondrial Respiration in the Large Cerebral Arteries in Rats With Type 2 Diabetes
The involvement of mitochondria in the pathophysiology of the metabolic syndrome is unclear. We have previously shown that mitochondrial respiration levels assessed by the Seahorse XFe24 analyzer in large cerebral arteries, and mitochondrial protein levels measure by western blot in cerebral microvessels, were similar in insulin resistant, non- diabetic, Zucker obese rats and lean control rats (Am J Physiol 310:H830-838, 2016). The objective of this study was to further investigate the dynamics of mitochondrial respiration and mitochondrial protein levels with the development of type II diabetes mellitus (T2DM). We studied the large cerebral arteries of 14 week old Zucker diabetic fatty obese rats (ZDFO) as a T2DM model and Zucker fatty lean rats (ZDFL) as non-diabetic controls. Body weight and blood glucose levels were significantly increased in ZDFO group compared with ZDFL group (347.2 ± 10.18 g vs. 320.4 ± 3.9 g, n = 20, P < 0.05; and 26.33 ± 1.56 mmol/L vs. 9.18 ± 0.46 mmol/L, n = 20, P < 0.05; respectively). We found that raw values for mitochondrial respiration were higher in the large cerebral arteries of ZDFL compared with ZDFO rats at all times. When we examined the individual, calculated parameters of respiration, we found that basal respiration and protein leak were higher in ZDFL compared with the ZDFO arteries (181.4 ± 10.93 pM/min/μg protein vs. 129.7 ± 8.211 pM/min/μg protein, n = 59, P < 0.05; and 149.3 ± 10.41 pM/min/μg protein vs. 100.3 ± 7.56 pM/min/μg protein, n = 59, P < 0.05; respectively). We have also found that the expression of the mitochondrial proteins, MnSOD, and the voltage-dependent anion channel (VDAC) was significantly lower in the cerebral microvessels of ZDFO rats (90.35 ± 9.13% vs. 123.1 ± 12.77%, n = 13, P < 0.05; and 23.63 ± 2.62% vs. 30.54 ± 2.07%, n = 12, P < 0.05; respectively). Our results show for the first time that mitochondrial dysfunction occurs relatively early in large cerebral arteries following the development of T2DM. Mitochondrial dysfunction likely contributes to cerebral vascular dysfunction and may lead to a mismatch between blood flow and metabolic demand in the brain.
Author Disclosures: I. Merdzo: None. I. Rutkai: None. P.V. Katakam: None. C.A. McNulty: None. S.V. Wunnava: None. D.W. Busija: None.
- © 2016 by American Heart Association, Inc.