Department of Haemostasis and Haemostatic Disorders, Chair of Laboratory Diagnostics, Medical University of Lodz, University Clinical Hospital No 2, Lodz, Poland.
Eur J Pharmacol. 2010 Aug 25;640(1-3):157-62. doi: 10.1016/j.ejphar.2010.05.014. Epub 2010 May 25.
1-methylnicotinamide (MNA) is a primary metabolite of nicotinamide. In recent years several activities of MNA have been described, such as anti-inflammatory activity in skin diseases, induction of prostacyclin synthesis via COX-2, aortal endothelium protection in diabetes and hypertriglyceridaemia and increasing survival rate of diabetic rats. The aim of the present study was to verify whether the increased survival rate of diabetic animals could be explained by anti-hyperglycaemic activity of MNA and/or by its protective effects on vascular endothelium. We used Sprague-Dawley male rats with an experimental streptozotocin diabetes. The animals received either MNA or pure drinking water. At the particular time intervals groups of rats were sacrificed and the blood was collected. We have shown that MNA increases levels of PGI2 in diabetic rats, but the effect is limited only to the early stage of diabetes. We were unable to prove anti-inflammatory effects of MNA, as it did not affect increased TNF-alpha in diabetic animals. We have confirmed our previous observations that MNA improved survival of diabetic animals, but contrary to our previous study, this effect was not accompanied by improvement in the parameters of long-term glycaemic control. Overall, we conclude that anti-diabetic activity of MNA manifested in the improved lifespan of diabetic animals is rather due to MNA pro-prostacyclin activity, and it may not be substantially related to glycaemic control in diabetes. Still other potential mechanism(s) await further elucidation.
1-甲基烟酰胺(MNA)是烟酰胺的主要代谢产物。近年来,人们描述了 MNA 的几种活性,如在皮肤病中的抗炎活性、通过 COX-2 诱导前列环素合成、在糖尿病和高三酰甘油血症中保护主动脉内皮以及提高糖尿病大鼠的存活率。本研究的目的是验证 MNA 对糖尿病动物的存活率的提高是否可以通过其降血糖活性和/或对血管内皮的保护作用来解释。我们使用雄性 Sprague-Dawley 大鼠进行实验性链脲佐菌素糖尿病。动物接受 MNA 或纯饮用水。在特定的时间间隔,处死大鼠组并收集血液。我们已经表明,MNA 增加了糖尿病大鼠中 PGI2 的水平,但这种作用仅限于糖尿病的早期阶段。我们无法证明 MNA 的抗炎作用,因为它不会影响糖尿病动物中 TNF-α的增加。我们证实了我们之前的观察结果,即 MNA 改善了糖尿病动物的存活率,但与我们之前的研究相反,这种作用并没有伴随着长期血糖控制参数的改善。总的来说,我们得出结论,MNA 的抗糖尿病活性表现在改善糖尿病动物的寿命,而不是由于 MNA 促前列环素活性,它可能与糖尿病中的血糖控制没有实质性关系。其他潜在的机制仍有待进一步阐明。