Anti-diabetic effects of 1-methylnicotinamide (MNA) in streptozocin-induced diabetes in rats.
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.
Watała
Cezary
C
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
Kaźmierczak
Piotr
P
Dobaczewski
Marcin
M
Przygodzki
Tomasz
T
Bartuś
Magdalena
M
Łomnicka
Magdalena
M
Słomińska
Ewa M
EM
Durackova
Zdena
Z
Chłopicki
Stefan
S
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
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