Quantitative Assay of Insulin Effect

Abstract

In the post-absorptive state the constancy of the blood sugar level is an expression of a well-maintained balance between glycogenolysis and the withdrawal of sugar from the blood stream. The fall of the blood sugar level subsequent to an injection of insulin is regarded as the result of an inhibition of the glycogenolytic process, the withdrawal of blood sugar going on unaltered. 1 , 2 , 3 The degree to which the blood sugar is lowered is not in direct proportion to the insulin dosage. 4 One may increase the insulin dosage considerably in the lower and higher ranges with little or no increase in the degree of blood sugar depression. The effect of the larger dose expresses itself in a maintenance of the maximum depression for a longer time period and in a slowing of the rate of return to the initial level. It follows that the effect of injected insulin lasts as long as the blood sugar is below the post-absorptive level. The quantitative determination of insulin action must, therefore, involve the measurement of both the intensity of blood sugar depression and its duration.

The times chosen by MacLeod and his coworkers 5 for determining blood sugar as a measure of insulin effect are suitable on the basis of the above postulate when relatively large doses are employed (0.5 units per kilo or over). Himsworth 6 has sought to measure the sensitivity of man to insulin by measuring the area enclosed by the depression curve below the resting level for the first 15 minutes. Scott and Dotti (loc. cit.) measured insulin response in terms of blood sugar depression at what they regard as optimum interval : 30 minutes after administration.