title: Anti-diabetic effects of 1-methylnicotinamide (MNA) in streptozocin-induced diabetes in rats.
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 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.
authors.affiliation: Department of Hemostasis and Hemostatic Disorders, Chair of Laboratory Diagnostics, Medical University of Łódź, University Clinical Hospital No 2, Poland. cwatala@csk.umed.lodz.pl
authors.forename: Cezary
authors.initials: C
authors.lastname: Watała
authors.forename: Piotr
authors.initials: P
authors.lastname: Kaźmierczak
authors.forename: Marcin
authors.initials: M
authors.lastname: Dobaczewski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Przygodzki
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bartuś
authors.forename: Magdalena
authors.initials: M
authors.lastname: Łomnicka
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Słomińska
authors.forename: Zdena
authors.initials: Z
authors.lastname: Durackova
authors.forename: Stefan
authors.initials: S
authors.lastname: Chłopicki
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010455:Peptides / Q000187:drug effects / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D015996:Survival Rate; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D009536:Niacinamide; D009569:Nitric Oxide; D010455:Peptides; D013311:Streptozocin; C050632:polypeptide C; C024058:N(1)-methylnicotinamide