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January 29, 1973

Diphenylhydantoin and Insulin-Secreting Tumors

JAMA. 1973;223(5):553-554. doi:10.1001/jama.1973.03220050053016

Originally intended and still used mainly for prevention of epileptic seizures, diphenylhydantoin has been shown to have multiple effects. One of these is hyperglycemia. After Belton and associates1 had induced hyperglycemia by diphenylhydantoin in rabbits (1965), there soon followed several reports of hyperglycemic hyperosmolar coma associated with diphenylhydantoin intoxication in man, and a report of glucose intolerance induced by conventional therapeutic doses of the drug.2 A number of in vitro studies on isolated rat pancreas are now providing insights into the mechanism of this hyperglycemic effect.

The immediate action of diphenylhydantoin was postulated by Millichap3 to be the stimulation of the hypothalamus with consequent hyperactivity of the sympathoadrenal system and its effects on the beta cell. Kizer et al4 suggested that diphenylhydantoin depresses the excitability of the beta cell and hence secretion of insulin by stimulating the Na-K-ATPase ("sodium pump") system with resulting reduction of intracellular