%0 Journal Article
%T Nicotinamide overload may play a role in the development of type 2 diabetes
%A Shi-Sheng Zhou
%A Da Li
%A Wu-Ping Sun
%A Ming Guo
%A Yong-Zhi Lun
%A Yi-Ming Zhou
%A Fu-Cheng Xiao
%A Li-Xin Jing
%A Shen-Xia Sun
%A Li-Bin Zhang
%A Ning Luo
%A Fu-Ning Bian
%A Wei Zou
%A Lai-Bin Dong
%A Zhi-Gang Zhao
%A Sheng-Fan Li
%A Xiao-Jie Gong
%A Zeng-Guo Yu
%A Chang-Bin Sun
%A Cong-
%J World Journal of Gastroenterology
%D 2009
%I Baishideng Publishing Group Co. Limited
%X 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 N1-methylnicotinamide on glucose metabolism, plasma H2O2 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 N1-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 ¡À 0.13 ¦̀mol/L vs 0.6 ¡À 0.13 ¦̀mol/L, P < 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N1-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N1-methylnicotinamide. Moreover, cumulative exposure to N1-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 N1-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 N1-methylnicotinamide clearance.CONCLUSION: These findings suggest that nicotinamide overload, which induced an increase in plasma N1-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.
%K Type 2 diabetes
%K Nicotinamide
%K N1-methylnicotinamide
%K Insulin resistance
%K Oxidative stress
%K Liver
%K Sweat glands
%U http://www.wjgnet.com/1007-9327/full/v15/i45/5674.htm