The B vitamin nicotinamide (NIC), commonly known as niacin, is currently in trial as a potential means-of preventing Type 1 diabetes in first-degree relatives of affected individuals. Sodium butyrate (BUT) a common dietary micronutrient has also been reported to have beneficial effects on the differentiation and function of pancreatic beta cells. Cultured rat insulin-secreting BRIN-BD11 cells were used to investigate the effects of 3 days exposure to NIC (10 mM) and BUT (1 mM) both alone and in combination on beta cell function. Culture with NIC and/or BUT resulted in reduction of growth, insulin content and basal insulin secretion. BUT additionally decreased cell viability whilst NIC had no significant effect. Treatment with either agent abolished beta cell glucose sensitivity but insulin secretory responsiveness to a wide range of beta cell stimulators, including a depolarizing concentration of K+, elevation of Ca2+ and activation of adenylate cyclase and protein kinase C, were enhanced. These data illustrate that long term exposure to NIC and BUT has both positive and negative effects on the function of insulin-secreting cells.