A Doubt for the Damage of Langerhan's Islets caused in the Alloxan, Dithizone and Oxine Diabetes

Abstract

Rabbits, rats and guinea pigs were singly administered with alloxan 200 mg/kg, dithizone 200 mg/kg and oxine 50-100 mg/kg respectively ; the blood sugar volue is measured 1.5, 3, 5, 8 10, 17, 24, 48 hours respectively after the injections. The animals were constantly of hyperglycemia by means of the chemical administration. Despite the effect of the chemicals was variably in degree with the kinds of animal, it was common to all animals that the temporary initial hyperglycemia is followed by the hypoglycemic status in 1-3 hours, and the severe hyperglycemia is successive.As the control to the chemical injection, another rabbits were administered with 40% hypertonic solution of glucose, 20 cc/kg/day for 7 days. The histological pictures of the islets were examined 24 hours after the injection ; according to the preparations of chromalume hematoxylin phloxin (CHP) stain, a majority of cells in islets appeared to be positive to phloxin (P) with the consequent impossibility for the identification of alpha-and beta-cells. In the latter, CH-positive granules or filamentous bodies decreased in number or almost disappeared. It was frequently encountered that the P-positive cylinderic elongated cells were arranged radially, as if it were a petal facing the capillary lumina, and the connective tissues concurrently grew in the adherences of the blood capillaries.In the temporary initial phase of hyperglycemia in rabbits administered with alloxan, CH-positive bodies did not so much decrease as by glucose administration. In spite of the expectation for the integral multiplication of them in the beta-cells in the hypoglycemia, they were, in fact, absent in 7 hours, which may deal with the releasing pattern from the cell-bodies gaining the subsequent strong affinity of P ; in 48 hours all of the cellular consistuents of islets were diffusively P-positive, in which were sometimes visible the aforementioned petal-like arrangement surrounding the closing lumina of the capillaries. Because of the comprehensive disappearance of CH-positive bodies, there were no longer the islets containing the typical beta-cells. Notwithstanding the profound hyperglycemia, any signs of degeneration in islet cells were not affirmative, at least the vanishment of the cellular elements following the necrosis and collapse or disintegration did not arise in the present observation. The histological changes in islets of rats with alloxan administration was same with those in rabbits. In particular, even when the animals were in the hyperglycemia in 48 hours, a small amount of CH-positive bodies were conservated in most of beta-cells, showing the fact that rats were not so much influenced by alloxan administration as rabbits. The alpha-cells accumulated in the peripheral layer of islet forming the syncytium became to have the apparent contour and to invade the internal areas of it by growing of cell population. The changes in guinea pigs corresponded in general to those in rabbits, where the pattern of the degeneration and collapse was also not visualized.Dithizone was capable to permit rabbits to fall into glycemia, in spite of the less effectiveness to the other animals. Morphological aspect of this compound to the islet cells resembled those of alloxan. However, it was a common observation that in the initial hyperglycemia in rabbits most of cells fall into the abnormal and augmented hyperplasia, whose cytoplasm was dense homogenous P-positive character on account of the releasing-out of CH-positive bodies. In the highest level of hyperglycemia caused after 48 hours, however, the patterns showing the considerable restoration from the inhibition of cell activity were present in a fashion that P-negative cells containing the numerous CH-positive bodies are commenced to take places in a certain locations of islets again. Of course, there were no signs involving in a degeneration or collapse in islets.