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.
| Original language | English |
|---|---|
| Pages (from-to) | 145-153 |
| Number of pages | 9 |
| Journal | Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy |
| Volume | 9 |
| DOIs | |
| State | Published - 10 May 2016 |
Fingerprint
Keywords
- Complex I
- Mitochondria
- Oxidative damage
- Oxidative stress
- Poly ADP ribosylation
- Polyol pathway
- Reactive oxygen species
- Sirtuins
Cite this
}
Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications. / Wu, Jinzi; Jin, Zhen; Zheng, Hong; Yan, Liang Jun.
In: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol. 9, 10.05.2016, p. 145-153.Research output: Contribution to journal › Review article
TY - JOUR
T1 - Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications
AU - Wu, Jinzi
AU - Jin, Zhen
AU - Zheng, Hong
AU - Yan, Liang Jun
PY - 2016/5/10
Y1 - 2016/5/10
N2 - 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.
AB - 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.
KW - Complex I
KW - Mitochondria
KW - Oxidative damage
KW - Oxidative stress
KW - Poly ADP ribosylation
KW - Polyol pathway
KW - Reactive oxygen species
KW - Sirtuins
UR - http://www.scopus.com/inward/record.url?scp=84968903168&partnerID=8YFLogxK
U2 - 10.2147/DMSO.S106087
DO - 10.2147/DMSO.S106087
M3 - Review article
AN - SCOPUS:84968903168
VL - 9
SP - 145
EP - 153
JO - Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
JF - Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
SN - 1178-7007
ER -