Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications

Jinzi Wu,1Zhen Jin,1Hong Zheng,1,2Liang-Jun Yan1 1Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USA; 2Department of Basic Theory of Traditional Chinese Medicine, College of Basic Medicine, Shandong University o...

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Autores principales:	Wu J, Jin Z, Zheng H, Yan LJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	diabetes NADH/NAD+ redox imbalance polyol pathway poly ADP ribosylation sirtuins oxidative stress oxidative damage Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/008ea9ba8d7d42fdadefcf36fbd3d272
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spelling	oai:doaj.org-article:008ea9ba8d7d42fdadefcf36fbd3d2722021-12-02T00:39:44ZSources and implications of NADH/NAD+ redox imbalance in diabetes and its complications1178-7007https://doaj.org/article/008ea9ba8d7d42fdadefcf36fbd3d2722016-05-01T00:00:00Zhttps://www.dovepress.com/sources-and-implications-of-nadhnad-redox-imbalance-in-diabetes-and-it-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Jinzi Wu,1Zhen Jin,1Hong Zheng,1,2Liang-Jun Yan1 1Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USA; 2Department of Basic Theory of Traditional Chinese Medicine, College of Basic Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China Abstract: NAD+ is a fundamental molecule in metabolism and redox signaling. In diabetes and its complications, the balance between NADH and NAD+ can be severely perturbed. On one hand, NADH is overproduced due to influx of hyperglycemia to the glycolytic and Krebs cycle pathways and activation of the polyol pathway. On the other hand, NAD+ can be diminished or depleted by overactivation of poly ADP ribose polymerase that uses NAD+ as its substrate. Moreover, sirtuins, another class of enzymes that also use NAD+ as their substrate for catalyzing protein deacetylation reactions, can also affect cellular content of NAD+. Impairment of NAD+ regeneration enzymes such as lactate dehydrogenase in erythrocytes and complex I in mitochondria can also contribute to NADH accumulation and NAD+ deficiency. The consequence of NADH/NAD+ redox imbalance is initially reductive stress that eventually leads to oxidative stress and oxidative damage to macromolecules, including DNA, lipids, and proteins. Accordingly, redox imbalance-triggered oxidative damage has been thought to be a major factor contributing to the development of diabetes and its complications. Future studies on restoring NADH/NAD+ redox balance could provide further insights into design of novel antidiabetic strategies. Keywords: mitochondria, complex I, reactive oxygen species, polyol pathway, poly ADP ribosylation, sirtuins, oxidative stress, oxidative damageWu JJin ZZheng HYan LJDove Medical PressarticlediabetesNADH/NAD+ redox imbalancepolyol pathwaypoly ADP ribosylationsirtuinsoxidative stressoxidative damageSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2016, Iss Issue 1, Pp 145-153 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetes NADH/NAD+ redox imbalance polyol pathway poly ADP ribosylation sirtuins oxidative stress oxidative damage Specialties of internal medicine RC581-951
spellingShingle	diabetes NADH/NAD+ redox imbalance polyol pathway poly ADP ribosylation sirtuins oxidative stress oxidative damage Specialties of internal medicine RC581-951 Wu J Jin Z Zheng H Yan LJ Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications
description	Jinzi Wu,1Zhen Jin,1Hong Zheng,1,2Liang-Jun Yan1 1Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USA; 2Department of Basic Theory of Traditional Chinese Medicine, College of Basic Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China Abstract: NAD+ is a fundamental molecule in metabolism and redox signaling. In diabetes and its complications, the balance between NADH and NAD+ can be severely perturbed. On one hand, NADH is overproduced due to influx of hyperglycemia to the glycolytic and Krebs cycle pathways and activation of the polyol pathway. On the other hand, NAD+ can be diminished or depleted by overactivation of poly ADP ribose polymerase that uses NAD+ as its substrate. Moreover, sirtuins, another class of enzymes that also use NAD+ as their substrate for catalyzing protein deacetylation reactions, can also affect cellular content of NAD+. Impairment of NAD+ regeneration enzymes such as lactate dehydrogenase in erythrocytes and complex I in mitochondria can also contribute to NADH accumulation and NAD+ deficiency. The consequence of NADH/NAD+ redox imbalance is initially reductive stress that eventually leads to oxidative stress and oxidative damage to macromolecules, including DNA, lipids, and proteins. Accordingly, redox imbalance-triggered oxidative damage has been thought to be a major factor contributing to the development of diabetes and its complications. Future studies on restoring NADH/NAD+ redox balance could provide further insights into design of novel antidiabetic strategies. Keywords: mitochondria, complex I, reactive oxygen species, polyol pathway, poly ADP ribosylation, sirtuins, oxidative stress, oxidative damage
format	article
author	Wu J Jin Z Zheng H Yan LJ
author_facet	Wu J Jin Z Zheng H Yan LJ
author_sort	Wu J
title	Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications
title_short	Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications
title_full	Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications
title_fullStr	Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications
title_full_unstemmed	Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications
title_sort	sources and implications of nadh/nad+ redox imbalance in diabetes and its complications
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/008ea9ba8d7d42fdadefcf36fbd3d272
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Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications

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