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

• Published in: World journal of gastroenterology : WJG Vol. 15; no. 45; pp. 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: Journal Article
• Language: English
• Published: United States The WJG Press and Baishideng 07.12.2009
• 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; Type 2 diabetes; Oxidative stress; Liver; Insulin resistance; Nicotinamide; Sweat glands; N~1-methylnicotinamide
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.15.5674

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.