On the development of alloxan diabetes in mice

Abstract

The development of alloxan diabetes in non-fasting mice of the NMRI strain was studied by measuring blood glucose, immunoassayable insulin. and liver glycogen levels. In addition the effects of tolbutamide and anti-insulin serum injections were studied. The results were as follows: 1) The initial hyperglycaemic phase following alloxan injection was accompanied by a highly significant decrease in plasma insulin levels and liver glycogen levels. Tolbutamide had no effect on the initial hyperglycaemia when given 5 min after alloxan, but greatly reduced the initial blood sugar level increase when given 5 min before alloxan. 2) The hypoglycaemic phase was accompanied by a marked rise in plasma insulin levels, which in the early phase showed a negative correlation with blood glucose levels. Liver glycogen levels increased towards normal values. The injection of anti-insulin serum 2 hr before the onset of the expected hypoglycaemia not only abolished the hypoglycaemic phase but was followed by a hyperglycaemia which surmounted the initial phase. 3) During the development of the permanent hyperglycaemic phase (studied 24 and 48 hr after alloxan injection) plasma insulin levels decreased gradually to subnormal or immeasurable values. Liver glycogen levels were highest 24 hr after alloxan injection and decreased only slowly during the following day. After 26 days, however, liver glycogen levels in alloxan diabetic mice were significantly lower than in normal mice, 24 hr after alloxan injection plasma insulin and blood glucose levels were inversely correlated. This was not the case after 48 hr or more. 4) During the stage of manifest alloxan diabetes, tolbutamide still had a slight but significant blood sugar lowering effect irrespective of the severity of the diabetic condition. The findings give strong evidence in mice of the correctness of the hypothesis of Iversen (1974) that the three phases of alloxan diabetes development are mainly due to a) insulin deficiency, b) insulin surplus, and c) insulin lack. During the first (hyperglycaemic) phase, however, a direct effect of alloxan on the liver appears to be present.