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

In most normal beta cells Zn was located mainly in mature secretory granules, less on their encasing membranous sacs and often in the intrasaccu-lar empty spaces of developing granules. The metal was sometimes located on the endoplasmic reticulum. During 24 days of starvation, the content of Zn in islet beta cells gradual increased as the fasting state proceeded. The ultrastructure of these cells during starvation showed an intense decrease of protein synthesis. The electron dense granules became fibrillar and/or amorphous and appeared vesicular on the 7th day of starvation. The intracellular Zn occupied intersac-cular cytoplasmic spaces and appeared 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 hy-pergranulation 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. Most Zn 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.