James W. Prahl

Production of Alloxan Diabetes and Ketoacidosis in the Laboratory Rat

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.

Metabolism of Lactate in Alloxan Diabetic Acidosis

Normal and alloxan diabetic rats were injected with DL-lactate-l-C-14, DL-lactate-2-C-14 and L(+) lactate-l-C-14 and the total excretion of radioactivity determined. The uncontrolled diabetic rat expired about 15–20 per cent less C-14-O2 than the normal animals. The diabetic animals excreted about twice as much radioactivity in the urine as the normal animals; in these diabetic animals essentially all of the radioactivity was found in glucose. After evaluation of all the possible reasons for the difference in amount of C-14-O2 expired by normal and diabetic animals it was concluded that lactate is metabolized at essentially the same rate in both animals but that in the diabetic animal, a greater portion of the carbon atoms of lactate is incorporated into glucose and less converted to CO2.