Nicotinamide protects human beta cells against chemically-induced necrosis, but not against cytokine-induced apoptosis

Nicotinamide intervention trials are presently undertaken to prevent Type I (insulin-dependent) diabetes in high risk subjects. They are based on stud ies in rodents reporting nicotinamide protection against beta-cell injury i n vitro and in vivo. This study examines whether nicotinamide can protect h uman beta cells in vitro. At concentrations (2 and 5 mmol/l) to protect rat beta cells against necrosis by streptozotocin or hydrogen peroxide, nicoti namide prevents hydrogen peroxide-induced necrosis of human beta cells. As with rat beta cells, nicotinamide fails to protect human beta cells against apoptosis induced by a combination of the cytokines interleukin-1 beta, in terferon-gamma and tumour necrosis factor-alpha. In rat beta cells, nicotin amide (2 to 20 mmol/l) was also found to induce apoptosis, in particular du ring the days following its protection against necrosis; this cytotoxic eff ect was not observed with human beta cells. These data demonstrate that nic otinamide can protect human beta cells against radical-induced necrosis, bu t not against cytokine-induced apoptosis. This effect is not associated wit h a delayed apoptosis as in rat beta cells.