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.

Effects of N1-methylnicotinamide on oxidative and glycooxidative stress markers in rats with streptozotocin-induced diabetes mellitus

“…A negative correlation found between MNA dose and AGEs fluorescence level could suggest the possibility of better effect if higher dose of MNA is used. In our previous work 29 we have published the decrease in plasma lipid peroxides influenced by administration of MNA at the dose of 100 mg/kg of body weight, Here we have found significant correlations between concentrations of lipid peroxides 29 and AGEs levels in all studied groups. It is apparent under the conditions of diabetes mellitus that glycation and oxidation are closely related and they damage concurrently more types of biomolecules.…”

“…In the earlier study Watala et al 29 have observed a significant decrease in non-fasting glucose after treatment with MNA and a mild but significant decrease in HbA 1c and for the first time demonstrated that MNA possessed profound antidiabetic effect that could be linked to its vasoprotective activity.…”

Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis

“…Furthermore, in the initiation and early hepatitis, MNA release was linked to the energy deficit/impaired redox status in hepatocytes, while in a later phase, MNA release was rather linked to the systemic inflammation. Taking into consideration the known pharmacological activity of exogenous MNA [1][2][3][4][5][6][7][8][9][10] our data suggest that release of endogenous MNA might regulate initiation and progression of hepatitis.…”

“…When administered locally, MNA displayed anti-inflammatory effects in patients with skin diseases [3,4] and inhibited inflammatory cell infiltration in animal models of skin inflammation in vivo [5]. Furthermore, MNA possessed gastroprotective [6], neuroprotective [7,8] and anti-diabetic properties [9,10].…”

Insulin, pioglitazone and Zingiber officinale administrations improve proliferating cell nuclear antigen immunostaining effects on diabetic and insulin resistant rat testis

“…Blood samples were collected from the tail vein 48 hours after Streptozotocin injection to confirm hyperglycemia using Dextrostix Test Strips (Bayer Corporation, U.K.) following the glucose oxidase method (Hugget and Nixon, 1957). Streptozotocin administration was not prolonged for more than 4 weeks without treatment because the glycemic levels were very high, and as time passed the animals became weaker (Watala et al, 2009) and eventually resulted in mortality.…”