title: Nicotinamide overload may play a role in the development of type 2 diabetes.
abstract: OBJECTIVE
  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 H(2)O(2) 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 micromol/L vs 0.6 +/- 0.13 micromol/L, P < 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N(1)-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N(1)-methylnicotinamide. 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 H(2)O(2) levels. Decrease in NAD/NADH ratio and increase in H(2)O(2) 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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Basic Medical Sciences, Medical College, Dalian University, Dalian, Liaoning Province, China. zhouss@ymail.com
authors: Shi-Sheng
authors: SS
authors: Zhou
authors: Da
authors: D
authors: Li
authors: Wu-Ping
authors: WP
authors: Sun
authors: Ming
authors: M
authors: Guo
authors: Yong-Zhi
authors: YZ
authors: Lun
authors: Yi-Ming
authors: YM
authors: Zhou
authors: Fu-Cheng
authors: FC
authors: Xiao
authors: Li-Xin
authors: LX
authors: Jing
authors: Shen-Xia
authors: SX
authors: Sun
authors: Li-Bin
authors: LB
authors: Zhang
authors: Ning
authors: N
authors: Luo
authors: Fu-Ning
authors: FN
authors: Bian
authors: Wei
authors: W
authors: Zou
authors: Lai-Bin
authors: LB
authors: Dong
authors: Zhi-Gang
authors: ZG
authors: Zhao
authors: Sheng-Fan
authors: SF
authors: Li
authors: Xiao-Jie
authors: XJ
authors: Gong
authors: Zeng-Guo
authors: ZG
authors: Yu
authors: Chang-Bin
authors: CB
authors: Sun
authors: Cong-Long
authors: CL
authors: Zheng
authors: Dong-Ju
authors: DJ
authors: Jiang
authors: Zheng-Ning
authors: ZN
authors: Li
mesh_terms: D000328:Adult; D000368:Aged; D042931:Aldehyde Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D013542:Sweat / Q000737:chemistry; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D016877:Oxidants; D009243:NAD; D009536:Niacinamide; D006861:Hydrogen Peroxide; D042931:Aldehyde Oxidase; C024058:N(1)-methylnicotinamide