Cytotoxic action of methylglyoxal on insulin-secreting cells

Methylglyoxal is a spontaneous product of glucose metabolism which is known to have cytotoxic actions and to be present in raised concentrations in hy perglycaemia. It could therefore play an important role in glucose toxicity . We have investigated the cytotoxic effects of methylglyoxal on insulin-se creting cells, which are particularly sensitive to glucose toxicity. Methyl glyoxal caused a concentration dependent increase in the number of apoptoti c RINm5F cells within 4-6 hours. A similar effect was observed with rat pan creatic p-cells. tert-butylglyoxal, which is a poor substrate for the glyox alase pathway, exerted a similar, though more potent apoptotic action. Dexa methasone and NaF were also found to induce apoptosis in RINm5F cells. Flow cytometric analysis suggested a degree of necrosis in addition to apoptosi s resulting from treatment with methylglyoxal. The cytotoxic effect of meth ylglyoxal could contribute towards glucose toxicity in insulin-secreting ce lls. (C) 2001 Elsevier Science Inc. All rights reserved.