Modulation of streptozotocin-induced insulitis and hyperglycaemia in the mouse

Multiple low-dose injections of streptozotocin (SZ) induce a gradually developing hyperglycaemia and pancreatic insulitis in certain inbred mouse strains. In the present investigation nicotinamide, which is known to protect against SZ-induced diabetes, was given prior to a single diabetogenic dose of SZ to C57BL/KsJ mice. Nicotinamide protected against SZ-induced hyperglycaemia in the acute phase but 13 of the 18 animals in this group became diabetic during the second week of observation. Nine of these mice had insulitis, seven of which showed overt diabetes. Since nicotinamide increased the serum glucose concentration at the time of the SZ-administration ten minutes later, the possibility that glucose mediated the protective action was evaluated. Glucose-pretreatment, however, was found to potentiate the diabetogenic action of SZ. It is obvious from the present data that another type of diabetes than that induced by a single high dose of SZ can be evoked if the immediate B-cytotoxic effects of SZ are reduced. It may be speculated that islet B-cells of mice given nicotinamide before SZ, for a time retain SZ-induced DNA injuries, which may lead to the expression of neoantigens and an autoimmune reaction.