Production of Alloxan Diabetes and Ketoacidosis in the Laboratory Rat

Abstract

The synergistic action of dehydroascorbic acid and alloxan in producing a diabetes mellitus-like state in the laboratory rat is utilized. Results of this method, in which the diabetogenic agents are administered subcutaneously, are compared with those in a series of rats made diabetic by intravenously administered alloxan. With experience it is possible to produce diabetes in greater than 90 per cent of the animals by either technic. Approximately 55 per cent of the animals died in the first month after alloxanization; the major causes of death were drug toxicity and iatrogenic hyperinsulinism, in that order. With improvement in technic and control, the mortality in the first month decreased to approximately 30 per cent. Induction of ketoacidosis was attempted by simultaneous withdrawal of insulin and institution of a ketogenie (high fat) diet. By such a regimen, ketosis could be attained in 75 per cent or more of those diabetic animals tried, whereas the incidence of ketoacidosis was considerably lower. Insulin withdrawal and continuation of the routine (high carbohydrate) diet was followed by ketosisbut only sporadic ketoacidosis. The behavior of populations of diabetic laboratory rats is presented in graphic form.