The present experiments were designed to investigate the immediate action of streptozotocin upon the beta cell by measuring its effect upon glucose-induced release by isolated islets of Langerhans. The results demonstrated a dose-related inhibition of glucose-induced secretion during the first two hours of incubation, with the inhibition most marked in the second hour. The same level of inhibition was achieved in the second hour regardless of whether the drug was present for both hours or for just the first hour.
Nicotinamide showed a dose-related protection against the inhibitory action of streptozotocin whereas nicotinic acid did not. Further, nicotinamide showed a protective trend even when added one hour after streptozotocin—indicating that no irreversible change in the insulin secretory mechanism had been elicited over the first hour of incubation. An enhancement of glucose-induced secretion was observed with nicotinamide alone. Nicotinamide was not able to protect against the inhibitory action of mannoheptulose and the latter had no significant effect upon streptozotocin's action.
It is concluded that the early hyperglycemia induced by streptozotocin is the result of a direct action of streptozotocin on the beta cell and that the same biochemical lesion may be responsible for both the impairment of insulin secretion and eventual beta-cell destruction. Finally, the demonstration of a protective action of nicotinamide at the site of the beta cell suggests that the nicotinamide adenine dinucleotide (NAD) level of the beta cell may be critical for maintenance of normal function.