Studies on the hyperglycemic effect of diphenylhydantoin in normal golden hamsters

Injected intraperitoneally at a dose of 100 mg/kg body weight into normal hamsters, diphenylhydantoin (DPH) induces a marked increase in blood glucose accompanied by a significant decrease in plasma insulin and a significant increase in plasma glucagon. After administration of phentolamine (5 mg/kg), the hyperglycemic effects of DPH is markedly reduced but remains statistically significant, plasma insulin levels are unchanged and the DPH-induced rise in plasma glucagon is significantly inhibited. Propranolol pretreatment (5 mg/kg) does not affect the DPH-induced changes in blood glucose, plasma insulin and plasma glucagon. Previous administration of reserpine (5 mg/kg/day for two days) does not modify the hyperglycemic response to DPH. These data suggest that the hyperglycemic action of DPH results from both a direct inhibitory effect of this compound on insulin secretion by the beta-cells and a direct stimulatory effect on glucagon secretion by the alpha-cells.