Morphologic effects of diazoxide and diphenylhydantoin on insulin secretion and biosynthesis in B cells of mice.

The action of diazoxide, an antidiuretic agent, and diphenylhydantoin, an antiepileptic (DPH), both with strong hyperglycemic side effects on the pancreatic B cells, was examined by electron microscopy and cytochemistry, with the following findings. 1. Effects on secretory apparatus: the severe hyperglycemic syndrome following a single injection of diazoxide (200 mg/kg) or DPH (150 mg/kg) did not change the granularity of the B cells. Ultrastructurally a marked increase of lysosomal digestion of secretory granules (crinophagy) was observed in almost all B cells. Crinophagy may be regarded as a result of an impaired discharge of secretory granules during simultaneous maintenance of biosynthesis. It is also possible that changes of the electrophysical properties of the granule surfaces may play an additional role in crinophagy. 2. Effect on synthesizing apparatus: in B cells subtotally degranulated by the injection of anti-insulin serum (AIS), regranulation occurred more rapidly after the additional administration of diazoxide or DPH than without these compounds. This fact may imply that, under the hyperglycemic conditions tested, diazoxide or DPH have no effect on the synthesizing capacity of the B cells.