The Effects of Alloxan on the Histology of the Pancreas, Thyroid and Adrenal Glands of the White Rat

Introduction: Prior to 1943, two methods of producing experimental diabetes mellitus in laboratory animals were known, pancreatectomy and the injection of anterior pituitary extract. In that year, the discovery of a third method, the destruction of the pancreatic islands of Langerhans by the intravenous injection of alloxan, was announced by Dunn, Sheehan and McLetchie. These workers were conducting an investigation into the pathogenesis of the renal lesion of the crush syndrome and the similar condition which occurs in mis-matched blood transfusions. Substances were being tried which influence the lower renal tubules, such as uric acid and related compounds. Among the most promising was alloxan, an oxidation product of uric acid. However, with the dosages required to obtain the renal lesions, many of the rabbits died during the first day or so with symptoms which could not be related to kidney damage. In the examination of these early mortalities, they discovered the characteristic lesion of the islets, and further investigation gave them rabbits exhibiting the typical tri-phasic blood sugar picture, with permanent diabetes resulting.