Characteristics of nicotinamide and N1-methylnicotinamide protection from alloxan diabetes in mice.

Comparisons were made of the dose-response and time-course characteristics of nicotinamide (NIC) and its metabolite, N1-methylnicotinamide (MNIC), protection from alloxan-induced diabetes in mice. A significant reduction in the permanent hyperglycemia caused by alloxan (50 mg/kg, iv) was observed when NIC or MNIC was given iv at a dose of 800 mg/kg 2 hr before alloxan. Complete protection was provided by pretreatment with 1200 mg/kg of either agent. There was a linear increase in 2-hr serum levels of NIC or MNIC after increasing doses of each protective agent. Protection after a 1200 mg/kg dose of NIC was of a shorter duration (6 hr) than after a corresponding dose of MNIC (greater than 24 hr). This longer protective action of the metabolite was accompanied by correspondingly higher serum levels of MNIC when compared to levels of NIC after an identical dose. No protective effects of NIC or MNIC were apparent when the agents were added to isolated mouse pancreatic islets prior to alloxan exposure in vitro. The results indicate that both NIC and its metabolite, when given in high doses before alloxan, are capable of protecting mice from alloxan diabetes. The protective action of NIC and MNIC appears to be an indirect one because the agents were ineffective as protectants in an in vitro system.