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

Autor: Sudhi Tyagi, Amberly Anger, Jingli Wang, Kathryn Repp, Michael E. Widlansky, Venkata K. Puppala, Mamatha Kakarla, Rong Ying
Rok vydání: 2019
Předmět:
Male
lcsh:Diseases of the circulatory (Cardiovascular) system
Brachial Artery
Endocrinology
Diabetes and Metabolism
Vasodilation
Pilot Projects
Type 2 diabetes
030204 cardiovascular system & hematology
Mitochondrion
0302 clinical medicine
Leukocytes
Uncoupling Protein 2
Prohibitin
Brachial artery
Inner mitochondrial membrane
Original Investigation
chemistry.chemical_classification
Membrane Potential
Mitochondrial
0303 health sciences
Middle Aged
Mitochondria
medicine.anatomical_structure
Female
Mitochondrial membrane potential
Cardiology and Cardiovascular Medicine
Adult
UCP2
medicine.medical_specialty
Endothelium
PHB
03 medical and health sciences
Internal medicine
medicine.artery
Prohibitins
medicine
Humans
030304 developmental biology
Aged
Reactive oxygen species
business.industry
medicine.disease
Repressor Proteins
Endocrinology
chemistry
Diabetes Mellitus
Type 2
lcsh:RC666-701
Case-Control Studies
business
Biomarkers
Zdroj: Cardiovascular Diabetology
Cardiovascular Diabetology, Vol 18, Iss 1, Pp 1-11 (2019)
ISSN: 1475-2840
Popis: 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.
Databáze: OpenAIRE
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