Electron microscopic studies on the secretory mechanism of pancreatic islet cells, with particular reference to beta cells. II. Secretion of beta granules in islets of Langerhans, particularly in association with intracellular reactive zinc under normal conditions, during prolonged starvation, and after administration of dithizone in rabbits.

Abstract

The intracellular sites of reactive zinc in cells of the islets of Langerhans, especially beta cells, were observed in rabbits by electron and light microscopy and correlated with granule synthesis, storage and discharge under normal conditions, during prolonged starvation and after dithizone administration. In most normal beta cells the metal was located mainly in mature secretory granules, less on their encasing membranous sacs and often in the intrasaccular empty spaces of developing granules. In a few instances, the metal was located on the endoplasmic reticulum. During 24 days of starvation, the content of histochemically demonstrable zinc in islet beta cells showed a gradual increase as the fasting state proceeded. The ultrastructure of the beta cells in the islets of Langerhans during starvation showed an intense decrease of protein synthesis as it progressed. The granules with distinct electron density began to become fibrillar and/or amorphous and to appear vesicular on the 7th day of starvation. The intracellular zinc began to occupy rather intersaccular cytoplasmic spaces and to appear on the surface of encasing sacs which did not contain the storage form of secretory granules. Near the end of fasting the metal was found in considerable amounts in the intersaccular cytoplasm, as well as on the surrounding membranous sacs. The earliest effect of dithizone was a transient hypergranulation in beta cells followed by the appearance of sacs containing remnants of granules and fibrillar and/or amorphous materials, and finally by disintegration of the surrounding membranous sacs. Various processes of degeneration and necrotization were seen during the first 24 hrs. After 4 days, the beta cells, which were less damaged, appeared hypoactive. The above findings suggest that most of zinc may intrude into maturing granules via their surrounding sacs derived from the Golgi lamellae and form the storage type of secretory granules under interaction of insulin with other combining proteins.