Further observations on the effects of alloxan on the pancreatic islets

Abstract

In the accounts which have been given [Dunn, McLetchie & Sheehan, 1943;Dunn, Kirkpatrick, McLetchie & Telfer, 1943] of the finding of necrosis of the pancreatic islets after intravenous injection of alloxan in rabbits, it was pointed out that this lesion came to light only because of the unexpected deaths at 12-48 hr. of certain of the animals so treated. Later it was recognized that such deaths were preceded by hypoglyeaemia and hypothermia, and sometimes by convulsions as had been observed by Jacobs [1937]. The doses which gave fatal results were usually relatively large, 200-300 mg./kg. body weight, but it was known, from experiments done prior to finding the islet lesions, that similar deaths might occur, though rarely, after a much smaller dose, in one case 25 mg./kg. On the other hand, somne rabbits had survived for more than 48 hr. doses of 300 and even 500 mg./kg., given on 1 day, without it being realized from ordinary observation that they had pfassed through a critical phase. As the pancreas was not examined in these animals the condition of the islets was not ascertained, nor was any alteration of the blood sugar suspected. Once the lesion of the islets had been found it appeared desirable that further information should be obtained as to the conditions of its occurrence and its pathogenesis, and it has been possible to carry out some experiments with this in view. These experiments have combined general observations on the animals and estimations of blood sugar with histological examination of the pancreas, and have been intended to find answers to three main questions: (1) the frequency of occurrence of islet necrosis after single intravenous doses of alloxan such as have been known to produce it; (2) the rate of development of necrosis from the earliest stages, and (3) the effects, if any, of smaller doses. EXPERIMENTSThe rabbits used were bf various breeds. They were kept in metabolism cages and their usual daily food was 150 g. each of oats and bran, mixed with 200 c.c. water. About 150 g. cabbage was also given daily with rare lapses due PH. CIII.

Thymic microenvironmental alterations in experimentally induced diabetes

“…Alloxan has been known for about six decades to induce diabetes mellitus in animals by causing a rather selective necrosis of insulin-producing cells (Dunn et al, 1944). Also, it has already been noted that this diabetogenic agent does not alter the viability of splenocytes and thymocytes, and so, this model would represent the better model to study the immune system in diabetes condition (Gaulton et al, 1985).…”

Alloxan: history and mechanism of action

“…It was by now clear that damage to the islet tissue was confined to the insulin secreting pancreatic B cells [14] through a direct effect [15], the A cells being resistant to alloxan [16]. Thus, alloxan proved to be a suitable compound for inducing experimental diabetes in animals: and has contributed greatly since to the study of diabetes.…”

Streptozotocin is responsible for the induction and progression of renal tumorigenesis in diabetic Wistar-Furth rats treated with insulin or transplanted with agarose encapsulated porcine islets

“…24 Alloxan (2,4,5,6-tetraoxypyrimidine; 5,6-dioxyuracil) was first reported to induce islet necrosis in rabbits by Dunn et al in 1943, 25 and can be administered intravenously, intraperitoneally or subcutaneously. Alloxan specifically destroys the insulinproducing beta cells of the islets of Langerhans while preserving the glucagon-secreting alpha cells, 26 which is analogous to the islet pathology of Type I diabetes.…”