Anti-diabetic effects of 1-methylnicotinamide (MNA) in streptozocin-induced diabetes in rats
Anti-diabetic effects of 1-methylnicotinamide (MNA) in streptozocin-induced diabetes in rats
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DOI：
10.1016/s1734-1140(09)70010-6
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发表时间：
2009-01-01
影响因子：
4.4
通讯作者：
Chlopicki, Stefan
中科院分区：
文献类型：
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作者：
Watala, Cezary;Kazmierczak, Piotr;Chlopicki, Stefan
1-甲基烟酰胺（MNA）是烟酰胺的主要内源性代谢产物，具有抗血栓和抗炎活性，并逆转内皮功能障碍。在目前的工作中，我们调查是否这样的血管保护的MNA活性提供抗糖尿病的行动在rates.Diabetes诱导链脲佐菌素（STZ）在Sprague-Dawley大鼠。在未治疗或MNA治疗的大鼠（每天100 mg/kg）注射STZ后8周，分析糖尿病的发展（空腹和非空腹血糖、HbA（1c）、肽C的血浆浓度）、氧化应激的发展（脂质过氧化、血浆蛋白的羰基化）以及主动脉、冠状动脉和肠系膜血管中NO依赖性内皮功能。最后，确定了MNA长期治疗对糖尿病大鼠长期生存的影响，MNA长期治疗显著降低了血浆中的空腹血糖浓度，对血浆HbA（1c）和肽C浓度有轻度影响，而对非空腹血糖没有影响。另一方面，MNA治疗大大降低脂质过氧化，蛋白质羰基化，完全防止损伤内皮依赖性血管舒张的主动脉中，完全由NO介导，但未能影响内皮功能的阻力血管，这是介导的只有部分NO。最重要的是，长期治疗MNA延长糖尿病大鼠的长期生存。总之，MNA显示出显著的抗糖尿病作用，这可能与其血管保护活性有关。
1-Methylnicotinamide (MNA), a major endogenous metabolite of nicotinamide, possesses anti-thrombotic and anti-inflammatory activity, and reverses endothelial dysfunction. In the present work, we investigated whether such a vasoprotective profile of MNA activity affords anti-diabetic action in rats.Diabetes was induced by streptozotocin (STZ) in Sprague-Dawley rats. Eight weeks after STZ injection in untreated or MNA-treated rats (100 mg kg(-1) daily), development of diabetes (plasma concentrations of fasting and non-fasting glucose, HbA(1c), peptide C), development of oxidant stress (lipid peroxidation, carbonylation of plasma proteins), as well as NO-dependent endothelial function in aorta, coronary and mesenteric vessels were analyzed. Finally, the effect of chronic treatment with MNA on long-term survival of diabetic rats was determined.Chronic treatment with MNA profoundly lowered fasting glucose concentrations in plasma, displayed mild effects on plasma HbA(1c) and peptide C concentrations, while having no effects on non-fasting glucose. On the other hand, MNA treatment considerably lowered lipid peroxidation, protein carbonylation, completely prevented impairment of endothelium-dependent vasodilatation in the aorta that was mediated entirely by NO, but failed to affect endothelial function in resistant vessels, which was mediated only partially by NO. Most importantly, chronic treatment with MNA prolonged the long-term survival of diabetic rats. In conclusion, MNA displayed a significant anti-diabetic effect that may be linked to its vasoprotective activity.