Streptozotocin-induced Diabetes and Islet Cell Alterations in Rabbits

Abstract

Rabbits are demonstrated to be susceptible to the dia-betogenic and B cell cytotoxic effects of streptozotocin. A single intravenous dose of 300 mg./kg. results in more marked and consistent B cell lesions than 150 or 75 mg./kg. but with greater lethal toxicity after eighteen hours. Animals surviving forty-eight hours or longer show marked hyperglycemie. Although serially progressive B cell alterations are noted both by light and electron microscopy, they are not uniform in any one pancreas or at any one time. Some B cells show necrobiosis with nuclear pyknosis within two hours after drug administration. However, most B cell nuclei show early aggregation of chromatin, rarefaction of interchromatinic material with nuclear enlargement and loss of typical nucleoli. This is followed by nuclear pyknosis with shrinkage and compression of content and eventual loss of chromatin with karyorrhexis by eighteen to twenty-four hours. Cytoplasmic changes at two to four hours include proliferation of ergastoplasm and ribosomes, the appearance of electronlucent regions of hyaloplasm at the secretory pole and mitochondrial swelling. Later there is dilatation of cisternae of endoplasmic reticulum, the appearance of electron dense intramitochondrial matrical aggregates and the breakdown of intercellular membranes. B cell granules persist until the cells begin to disintegrate. Streptozotocin was also found to induce necrobiosis in occasional A cells but no effect could be detected on D cells.