Streptozotocin Diabetes: Time Course of Irreversible B-Cell Damage; Further Observations on Prevention by Nicotinamide

Further studies on the mode of action of streptozotocin and the prevention of its effects by nicotinamide have yielded the following results: 1. The injection of nicotinamide at varying time intervals after streptozotocin afforded partial protection against its β-cytotoxic effects, decreasing with the length of the intervals but still significant when the interval was 2 hr. 2. Manno-heptulose failed to suppress the insulin release occurring between 6 and 10 hr after the injection of streptozotocin. 3. Nicotinic acid administered by gastric tube failed to protect against the diabetogenic effect of streptozotocin. 4. Nicotinamide injected 10 min after alloxan afforded no protection against the diabetogenic effect of the latter. It is concluded (1) that the β-cytotoxic effect of streptozotocin is not immediately irreversible or that it does not affect all B-cells simultaneously; (2) that the insulin release observed between 6 and 10 hr after the injection of streptozotocin occurs by way of leakage from damaged B-cells; (3) that the ineffectiveness of nicotinic acid in preventing the β-cytotoxic effect of streptozotocin is probably not the consequence of its insufficient conversion to nicotinamide after parenteral administration; and (4) that streptozotocin and alloxan differ in their mechanism of action on the pancreatic B-cell.