Inhibition of Insulin Secretion by Diphenylhydantoin in the Isolated Perfused Pancreas

Abstract

To investigate the mechanisms involved in the production of hyperglycemia by diphenylhydantoin (DPH), rat pancreases were extirpated and perfused with 75 μg/mlof this drug. The insulin response to glucose was compared in DPH-perfused and control organs. DPH completely inhibited the immunoreactive insulin response to glucose. There was no effect upon the standard immunoassay curve for insulin by DPH. These findings imply that DPH-induced hyperglycemia results from direct impairment of insulin secretion. The mechanism for this may be related to an alteration of cellular sodium transfer by DPH.