Serial alterations in blood glucose of normal and adrenalectomized mice following the administration of a diabetogenic dose of streptozotocin have been compared with those of similar mice pretreated with nicotinamide. An initial hyperglycemic phase, one to three hours post-injection, was observed with both streptozotocin and nicotinamide treated mice, and was drug related. In the case of streptozotocin the early elevation in blood sugar was not dependent on the presence of the adrenal gland. An initial hyperglycemic phase was recorded in fed adrenalectomized mice but was eliminated in fasted adrenalectomized mice because of decreased liver glycogen. A hypoglycemic phase at seven hours was observed with streptozotocin treatment. This was associated with a seven-fold increase in plasma immunoreactive insulin (IKI) concentration observed in streptozotocin treated normals. By twenty-four hours the streptozotocin treated mice were permanently diabetic, and had significantly depressed pancreatic insulin concentrations, while plasma insulin was still greater than control concentrations. The nicotinamide protected group demonstrated no evidence of diabetes. The mechanism of diabeto genesis of streptozotocin differs from that of alloxan.

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