Pancreatic B cells possess defense mechanisms against cell-specific toxicity

Insulin-dependent diabetes develops when more than 90% of the insulin containing B cells are destroyed. The present study investigates whether the target B cells can counteract the damaging effects of cytotoxic substances. Purified islet cells were first exposed for 3-10 min to t-butylhydroperoxide, alloxan, streptozotocin, or B-cell surface antibodies plus complement, then cultured for 20 hr before the percent of dead cells was counted. t-Butylhydroperoxide destroyed all islet cell types whereas the three other agents exerted a dose-dependent toxicity upon islet B cells only. The survival of drug- and complement-treated cells varied with the culture conditions present between the initial cellular attack and the moment of cell death. For the four B-cell toxic agents tested, an increase in medium glucose following any of these treatments reduced the percent of dead cells. This protective effect was not observed with galactose or fructose, nor could it be induced in islet non-B cells; it was additive to the protective action glucose induced during preincubation of the cells prior to their exposure to certain cytotoxic agents such as alloxan. Nicotinamide also enhanced the survival of drug-treated B cells, irrespective of the damaging compound. The vitamin was most effective when applied immediately after the initial drug or complement treatment; it also protected islet non-B cells--in contrast to glucose. The present in vitro study has led to the recognition of defense mechanisms in pancreatic B cells. Physiologic compounds such as glucose and nicotinamide were found to stimulate islet B cells to counteract the damaging effects of B-cell toxic conditions. It is conceivable that the events involved in this protection are implicated in the pathogenesis and/or prevention of insulin-dependent diabetes.