Ultrastructural Pancreatic Beta-Cell Changes in Rabbits After Small and Large Doses of Alloxan

Abstract

The effect of a single injection of alloxan monohydrate, varying in dosages from 12.5 to 200 mg./kg. body weight, on the ultrastructure of pancreatic β cells was investigated in 100 adult rabbits killed five minutes to fourteen days after alloxan administration. Large doses of alloxan (50 to 200 mg./kg.) produced severe hyperglycemia due to marked β-cell damage characterized by translucent areas in the hyaloplasm, mitochondrial swelling, disintegration of the intercellular membrane, and nuclear pyknosis, followed by the dissolution of β- cell granules and, ultimately, disintegration of the cell. The sequence in which these changes occur suggests that alloxan, in high dosages, exerts its principal damaging action, at least initially, upon the paramembranous portion of the β-cell cytoplasm. After small doses of alloxan, 12.5 or 25 mg./kg., hyperglycemia failed to occur. In these animals there was early degranulation, distension of the cisternae of the endoplasmic reticulum, variable dilatation of the profiles of the Golgi apparatus, and formation of morphologically atypical β-cell granules. Small doses of alloxan, while not destroying the pancreatic β cells, alter the β-cell secretory apparatus sufficiently to induce subdiabetes, so that a normally nondiabetogenic dose of cortisone (1 mg./kg.) converts this state into one of overt diabetes. The ultrastructural and functional pancreatic β-cell changes after small doses of alloxan alone are quite similar to those induced by large doses of alloxan in cortisone-pretreated rabbits.