Hypoglycemic Action of Alloxan

The study of the physiological regulation of blood-sugar concentration embraces a complexity of independently variable factors whose individual influences are still incompletely understood. Many experimental substances and conditions will cause hyperglycemia, but none besides insulin are known which will cause hypoglycemia.

Alloxan will produce hypoglycemia in normal rabbits in a very characteristic fashion. If upwards of 70 mg. of alloxan monohydrate per kg. of body weight is injected intravenously the blood sugar level of the animal will fall below the normal value (less than 70 mg. %) in about 3-4 hours, and will continue to fall steadily during the next 2-4 hours until the convulsive level (less than 35 mg. %) is reached. It will keep falling further during the convulsive stage until the animal expires, and very low (less than 15 mg. %) values may be observed terminally. All normal rabbits respond in the same way, although some delay in the time of onset of convulsions is observed if the animals have not fasted for 12-24 hours before the experiment. The larger dosages of alloxan (150-200 mg./kg.) will not hasten the appearance of convulsions, but will very definitely cause the recurrence of convulsions after remissions induced by glucose.

Both the convulsions and the hypoglycemia are promptly relieved by glucose intravenously administered. Animals in violent convulsions will return to a conscious and quite normal state within one minute after glucose has been given. After 5-10 minutes they will eat and drink in a normal manner. If the dosage of alloxan has been large hypoglycemia and convulsions may recur several times at intervals of 2-3 hours provided that each attack is treated with glucose. Large dosages of glucose or sufficient food intake tend to forestall subsequent seizures.