Using the method of glucose-1-14C oxydation to 14CO2 on the rat epididymal adipose tissue, the insulin-like activities (ILA) in the serum have been compared before and after oral loading with glucose in normal subjects, in maturity-onset diabetics and in insulin-requiring diabetics. In maturity-onset diabetics mean fasting values were found to be 30% below normal while in insulin-requiring diabetics they were 85% above normal. In normal subjects there was observed, 30 minutes after glucose loading, a moderate increase in blood sugar together with an increase of ILA of 222% above the starting value; in maturity-onset diabetics the increase in ILA was only 106% while the blood sugar was markedly increased. After glucose loading in maturity-onset diabetics, the total amount of insulin detected during the period of the experiment was, on the average, only 45% of that found in normal subjects. In insulin requiring diabetics there was no increase but, on the contrary, a steady decrease of the ILA values, while the blood sugar excessively increased. In general ILA values were higher than those in maturity-onset diabetics. No difference in response was found between maturity-onset diabetics treated with diet alone and those treated with diet and oral hypoglycaemic drugs. In contrast to the absolute ILA values, the index of insulin reserve, is of value in assessing the functional capacity of the pancreas. This index decreases progressively with the severity of the disease and reaches a maximum of 54% of the normal in maturity-onset diabetics, which can satisfactorily be explained by pancreas insufficiency.
Only in some cases of insulin-requiring diabetics was an insulin reserve still detectable. The biological inactivity of the insulin circulating in the blood can be deduced from the increased ILA-values, as compared with those found in maturity-onset diabetics. Obviously some of this insulin can be released by the addition of glucose. It is likely that, in addition to pancreatic insufficiency, insulin-binding or insulin-inactivating antibodies play a part in the pathogenesis of insulin-requiring diabetes.