Studies on the mechanism of alloxan hypoglycemia.

It is well known that when alloxan is injected intravenously into rabbits, dogs, and monkeys an initial hyperglycemia is followed by a transient hypoglycemia, leading to death of the animals from hypoglycemic convulsions. If the hypoglycemia is prevented by repeated intravenous injections of glucose, the animals survive and permanent hyperglycemia and diabetes develop. The cause of the transient hypoglycemia has been differently explained by different workers. While Goldner and Gomori (l), Ridout et al. (2), Kennedy and Lukens (3), and Banerjee (4) consider that the alloxan hypoglycemia is pancreatic in origin owing to the release of preformed insulin from the necrosed islets, Houssay et al. (5), Wrenshall (G), and Carrasco-Formiguera (7) are of opinion that the cause of this hypoglycemia is extrapancreatic. In experiments with dogs Houssay et al. (5) observed hypoglycemia when alloxan was injected half an hour after the animals were pancreatectomized. Wrenshall (6) removed the pancreas of dogs 9 hours after the animals had received injections of a diabetogenic dose of alloxan and determined its insulin content. No significant difference in the insulin content as compared to normal controls was observed, which indicated that no measurable quantity of insulin was released into the circulation. Wrenshall further observed that when dogs mere made resistant to insulin by injections of anterior pituitary extract a diabetogenic dose of alloxan significantly lowered the blood sugar level to that of normal controls. Carrasco-Formiguera (7) clamped the pancreaticoduodenal blood vessels in three dogs before the diabetogenic dose of alloxan was injected. Although all of the animals failed to develop diabetes, all showed pronounced hypoglycemia. In experiments with rabbits Carrasco-Formiguera observed that when rabbits received injections of epinephrine 1 hour prior to the injection of a diabetogenic dose of alloxan most of the animals failed to develop diabetes, but all of them had pronounced hypoglycemia. Goldner and Gomori (8) could not confirm the claims of Houssay and others (5-7). They observed no hypoglycemia after injection of diabetogenic doses of alloxan in dogs in which the pancreas was removed 30 minutes or several days or weeks prior to the injection. When the blood