STREPTOZOTOCIN AT LOW-DOSES INDUCES APOPTOSIS AND AT HIGH-DOSES CAUSES NECROSIS IN A MURINE PANCREATIC BETA-CELL LINE, INS-1

The ability of beta cells to endure assaults by various environmental agents, including toxins and viruses, may be relevant to the developme nt of diabetes. We have examined the mode of cell death caused by stre ptozotocin (STZ) in a murine pancreatic beta cell line, INS-1. Apoptos is was identified by detection of initial endonuclease-mediated DNA st rand breaks by DNA gel electrophoresis. Apoptosis and necrosis were di stinguished morphologically by light and electron microscopy. Higher r ates of apoptosis, as compared to necrosis, were observed when cells w ere exposed to 15 mM STZ for 1 hr followed by a 24 hrs recovery period . Higher doses of STZ (30 mM) caused the cells to undergo necrosis (22 %) as well as apoptosis (17%). These results suggest that the cytotoxi c effect of STZ, at low doses, on beta cells involves the activation o f the apoptotic pathway, whereas, at high doses, the mode of beta cell death is predominantly necrosis.