Anti-diabetic effects of 1-methylnicotinamide (MNA) in streptozocin-induced diabetes in rats Cezary Wata³a 1 , Piotr KaŸmierczak 1,2 , Marcin Dobaczewski 1,2 , Tomasz Przygodzki 1 , Magdalena Bartuœ 3 , Magdalena £omnicka 3 , Ewa M. S³omiñska 4 , Zdena Duraèkova 5 , Stefan Ch³opicki 3 1 Department of Hemostasis and Hemostatic Disorders, Chair of Laboratory Diagnostics, Medical University of £ódŸ, University Clinical Hospital No. 2, Poland 2 Postgraduate School of Molecular Medicine, Warszawa, Poland 3 Department of Experimental Pharmacology, Chair of Pharmacology, Jagiellonian University Medical College, Grzegórzecka 16, PL 31-531 Kraków, Poland 4 Department of Biochemistry, Medical University of Gdañsk, Gdañsk, Poland 5 Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovakia Correspondence: Cezary Wata³a, email: cwatala@csk.umed.lodz.pl, cwatala@toya.net.pl; http://www.interhemostaza.pl Abstract: 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 low- ered 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 par- tially 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. Key words: 1-methylnicotinamide, streptozotocin, experimental diabetes, endothelial dysfunction survival 86 Pharmacological Reports, 2009, 61, 86–98 Pharmacological Reports 2009, 61, 86–98 ISSN 1734-1140 Copyright © 2009 by Institute of Pharmacology Polish Academy of Sciences