Institute of Basic Medical Sciences, Medical College, Dalian University, Dalian, Liaoning Province, China.
World J Gastroenterol. 2009 Dec 7;15(45):5674-84. doi: 10.3748/wjg.15.5674.
To investigate whether nicotinamide overload plays a role in type 2 diabetes.
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.
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.
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.
探讨烟酰胺负荷是否在 2 型糖尿病中发挥作用。
采用高效液相色谱法比较 14 例糖尿病患者和 14 例非糖尿病患者的烟酰胺代谢模式。观察烟酰胺和 N(1)-甲基烟酰胺对成年 Sprague-Dawley 大鼠葡萄糖代谢、血浆 H(2)O(2)水平和组织烟酰胺腺嘌呤二核苷酸（NAD）含量的累积效应。分别采用桑拿和烧伤损伤研究人汗腺和大鼠皮肤在烟酰胺代谢中的作用。
与非糖尿病患者相比，负荷 100mg 烟酰胺 5 小时后，糖尿病患者的血浆 N(1)-甲基烟酰胺水平显著升高（0.89±0.13µmol/L 比 0.6±0.13µmol/L，P<0.001）。烟酰胺累积剂量（2g/kg）显著增加了大鼠血浆 N(1)-甲基烟酰胺浓度，导致严重胰岛素抵抗，这与 N(1)-甲基烟酰胺相似。此外，累积暴露于 N(1)-甲基烟酰胺（2g/kg）显著降低了大鼠肌肉和肝脏 NAD 含量和红细胞 NAD/NADH 比值，并增加了血浆 H(2)O(2)水平。体外暴露于 N(1)-甲基烟酰胺后，人红细胞的 NAD/NADH 比值降低和 H(2)O(2)生成增加也观察到。出汗可消除过量的烟酰胺（负荷 100mg 烟酰胺 1 小时后，汗液中烟酰胺浓度增加 5.3 倍）。皮肤损伤或醛氧化酶抑制（三苯氧胺或奥氮平）均因损害葡萄糖耐量而臭名昭著，会延迟 N(1)-甲基烟酰胺的清除。
这些发现表明，烟酰胺负荷增加，导致血浆 N(1)-甲基烟酰胺增加，与氧化应激和胰岛素抵抗有关，在 2 型糖尿病中起作用。
