Nicotinamide overload may play a role in the development of type 2 diabetes

AIM： To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS： Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N^1-methylnicotinamide on glucose metabolism, plasma HzO2 levels an...

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Published in:World journal of gastroenterology : WJG 2009-12, Vol.15 (45), p.5674-5684
Main Authors: Zhou, Shi-Sheng, Li, Da, Sun, Wu-Ping, Guo, Ming, Lun, Yong-Zhi, Zhou, Yi-Ming, Xiao, Fu-Cheng, Jing, Li-Xin, Sun, Shen-Xia, Zhang, Li-Bin, Luo, Ning, Bian, Fu-Ning, Zou, Wei, Dong, Lai-Bin, Zhao, Zhi-Gang, Li, Sheng-Fan, Gong, Xiao-Jie, Yu, Zeng-Guo, Sun, Chang-Bin, Zheng, Cong-Long, Jiang, Dong-Ju, Li, Zheng-Ning
Format: Article
Language:English
Subjects:
2型糖尿病
Adult
Aged
Aldehyde Oxidase - antagonists & inhibitors
Aldehyde Oxidase - metabolism
Animals
Blood Glucose - metabolism
Diabetes Mellitus, Type 2 - metabolism
Erythrocytes - metabolism
Female
Humans
Hydrogen Peroxide - metabolism
Insulin - metabolism
Male
Middle Aged
NAD - metabolism
Niacinamide - administration & dosage
Niacinamide - adverse effects
Niacinamide - analogs & derivatives
Niacinamide - metabolism
Original
Oxidants - metabolism
Random Allocation
Rats
Rats, Sprague-Dawley
Risk Factors
Sweat - chemistry
Young Adult
烟酰胺
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Summary:AIM： To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS： Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N^1-methylnicotinamide on glucose metabolism, plasma HzO2 levels and tissue nicotinamide adenine dinucleotide （NAD） contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS： Diabetic subjects had significantly higher plasma N^1-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects （0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P 〈 0.001）. Cumulative doses of nicotinamide （2 g/kg） significantly increased rat plasma Nl-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by Nl-methy-Inicotinamide. Moreover, cumulative exposure to N^1- methylnicotinamide （2 g/kg） markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H2O2 levels. Decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to N^1-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide （5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load）. Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N^1- methylnicotinamide clearance. CONCLUSION： These findings suggest that nicotinamide overload, which induced an increase in plasma N^1- methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.15.5674