Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation
Abstract Background Excessive reactive oxygen species from endothelial mitochondria in type 2 diabetes individuals (T2DM) may occur through multiple related mechanisms, including production of mitochondrial reactive oxygen species (mtROS), inner mitochondrial membrane (Δψm) hyperpolarization, change...
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doaj-dfd4ba76cce04178a547e91a404aeabe2020-11-25T04:09:58ZengBMCCardiovascular Diabetology1475-28402019-11-0118111110.1186/s12933-019-0956-4Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilationMamatha Kakarla0Venkata K. Puppala1Sudhi Tyagi2Amberly Anger3Kathryn Repp4Jingli Wang5Rong Ying6Michael E. Widlansky7Department of Medicine, Division of Cardiovascular Medicine, Medical College of WisconsinDepartment of Medicine, Division of Cardiovascular Medicine, Medical College of WisconsinDepartment of Medicine, Division of Cardiovascular Medicine, Medical College of WisconsinDepartment of Medicine, Division of Cardiovascular Medicine, Medical College of WisconsinDepartment of Medicine, Division of Cardiovascular Medicine, Medical College of WisconsinDepartment of Medicine, Division of Cardiovascular Medicine, Medical College of WisconsinDepartment of Medicine, Division of Cardiovascular Medicine, Medical College of WisconsinDepartment of Medicine, Division of Cardiovascular Medicine, Medical College of WisconsinAbstract Background Excessive reactive oxygen species from endothelial mitochondria in type 2 diabetes individuals (T2DM) may occur through multiple related mechanisms, including production of mitochondrial reactive oxygen species (mtROS), inner mitochondrial membrane (Δψm) hyperpolarization, changes in mitochondrial mass and membrane composition, and fission of the mitochondrial networks. Inner mitochondrial membrane proteins uncoupling protein-2 (UCP2) and prohibitin (PHB) can favorably impact mtROS and mitochondrial membrane potential (Δψm). Circulating levels of UCP2 and PHB could potentially serve as biomarker surrogates for vascular health in patients with and without T2DM. Methods Plasma samples and data from a total of 107 individuals with (N = 52) and without T2DM (N = 55) were included in this study. Brachial artery flow mediated dilation (FMD) was measured by ultrasound. ELISA was performed to measure serum concentrations of PHB1 and UCP2. Mitochondrial membrane potential was measured from isolated leukocytes using JC-1 dye. Results Serum UCP2 levels were significantly lower in T2DM subjects compared to control subjects (3.01 ± 0.34 vs. 4.11 ± 0.41 ng/mL, P = 0.04). There were no significant differences in levels of serum PHB. UCP2 levels significantly and positively correlated with FMDmm (r = 0.30, P = 0.03) in T2DM subjects only and remained significant after multivariable adjustment. Within T2DM subjects, serum PHB levels were significantly and negatively correlated with UCP2 levels (ρ = − 0.35, P = 0.03). Conclusion Circulating UCP2 levels are lower in T2DM patients and correlate with endothelium-dependent vasodilation in conduit vessels. UCP2 could be biomarker surrogate for overall vascular health in patients with T2DM and merits additional investigation.http://link.springer.com/article/10.1186/s12933-019-0956-4MitochondriaEndotheliumMitochondrial membrane potentialUCP2PHB |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mamatha Kakarla Venkata K. Puppala Sudhi Tyagi Amberly Anger Kathryn Repp Jingli Wang Rong Ying Michael E. Widlansky |
spellingShingle |
Mamatha Kakarla Venkata K. Puppala Sudhi Tyagi Amberly Anger Kathryn Repp Jingli Wang Rong Ying Michael E. Widlansky Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation Cardiovascular Diabetology Mitochondria Endothelium Mitochondrial membrane potential UCP2 PHB |
author_facet |
Mamatha Kakarla Venkata K. Puppala Sudhi Tyagi Amberly Anger Kathryn Repp Jingli Wang Rong Ying Michael E. Widlansky |
author_sort |
Mamatha Kakarla |
title |
Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation |
title_short |
Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation |
title_full |
Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation |
title_fullStr |
Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation |
title_full_unstemmed |
Circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation |
title_sort |
circulating levels of mitochondrial uncoupling protein 2, but not prohibitin, are lower in humans with type 2 diabetes and correlate with brachial artery flow-mediated dilation |
publisher |
BMC |
series |
Cardiovascular Diabetology |
issn |
1475-2840 |
publishDate |
2019-11-01 |
description |
Abstract Background Excessive reactive oxygen species from endothelial mitochondria in type 2 diabetes individuals (T2DM) may occur through multiple related mechanisms, including production of mitochondrial reactive oxygen species (mtROS), inner mitochondrial membrane (Δψm) hyperpolarization, changes in mitochondrial mass and membrane composition, and fission of the mitochondrial networks. Inner mitochondrial membrane proteins uncoupling protein-2 (UCP2) and prohibitin (PHB) can favorably impact mtROS and mitochondrial membrane potential (Δψm). Circulating levels of UCP2 and PHB could potentially serve as biomarker surrogates for vascular health in patients with and without T2DM. Methods Plasma samples and data from a total of 107 individuals with (N = 52) and without T2DM (N = 55) were included in this study. Brachial artery flow mediated dilation (FMD) was measured by ultrasound. ELISA was performed to measure serum concentrations of PHB1 and UCP2. Mitochondrial membrane potential was measured from isolated leukocytes using JC-1 dye. Results Serum UCP2 levels were significantly lower in T2DM subjects compared to control subjects (3.01 ± 0.34 vs. 4.11 ± 0.41 ng/mL, P = 0.04). There were no significant differences in levels of serum PHB. UCP2 levels significantly and positively correlated with FMDmm (r = 0.30, P = 0.03) in T2DM subjects only and remained significant after multivariable adjustment. Within T2DM subjects, serum PHB levels were significantly and negatively correlated with UCP2 levels (ρ = − 0.35, P = 0.03). Conclusion Circulating UCP2 levels are lower in T2DM patients and correlate with endothelium-dependent vasodilation in conduit vessels. UCP2 could be biomarker surrogate for overall vascular health in patients with T2DM and merits additional investigation. |
topic |
Mitochondria Endothelium Mitochondrial membrane potential UCP2 PHB |
url |
http://link.springer.com/article/10.1186/s12933-019-0956-4 |
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