The Interaction of Glucagon and Insulin on Blood Glucose

Abstract

In previous publications from this laboratory (1, 2) evidence was presented which indicates that glucagon enhances the peripheral utilization of glucose 1 in normal men and dogs as well as in the depancreatized dog. The purpose of this paper is to report experiments on the combined effect of glucagon and insulin on arterial and venous glucose levels in normal men, and to compare the magnitude of this effect with that observed in subjects given similar amounts of each hormone separately. ranging from 60 to 100 minutes. Insulin dosage ranged from 0.054 to 0.128 units per min. by constant intravenous infusion for periods ranging from 65 to 110 minutes. Mean insulin dosage for the subjects given insulin alone was .076 units per minute, for the subjects given insulin plus glucagon it was .071 units per minute. The dosage of insulin was arrived at by trial and error; the criteria used were that the dose be sufficient to cause a definite drop in blood sugar, but not so large as to result in hypoglycemic values. Data in which arterial blood sugar fell below 65 mg. per cent were discarded. In the subjects who received both insulin and glucagon, the insulin infusion was begun 15. to 25 minutes before the glucagon in order to obtain the maximum effect of each hormone (on blood sugar level) at approximately the same time. METHODS FiftyVenous and capillary (finger) blood specimens were drawn at five or ten-minute intervals, a total of 30 to 40 samples during each experiment Venous samples were obtained from the antecubital vein which carries mixed blood from the deep and superficial tissue of the forearm and hand (3,4). Capillary blood contains the same glucose concentration as arterial blood (5). Samples were analyzed for glucose content by the Nelson-Somogyi method (6). Sodium fluoride and immediate refrigeration were used to prevent glycolysis in the samples. Capillary samples were analyzed singly, venous samples in duplicate. In approximately 900 duplicate venous samples the maximum difference between any pair was 10 per cent, and the average was 2 per cent.The A-V/A data were subjected to a statistical analysis by means of a non-parametric median test (7); i.e., using the medians as a cutting point The data were placed in a 2 X 2 contingency table, and then subjected to a chisquare analysis. RESULTS

Influence of Thyroid Function on Carbohydrate Metabolism and a New Method for Assessing Response to Insulin

“…It is noteworthy that following administration of insulin, 2 of the 13 hypothyroid patients had C eq values below zero, whereas all of the 38 euthyroid and 15 hyperthyroid patients had C oq values above zero. We have also observed negative C eq values following administration of insulin in 7 of 32 patients with parenchymatous liver disease (41). Furthermore, in 14 of these 32 patients there was no increase in K value after administration of insulin, and the 7 patients with negative C eq values were all among the 14 who did not respond to insulin.…”

“…On the other hand, there is evidence which suggests that thyroid hormone accelerates the degradation of insulin in the rat (39,40) and our preliminary studies indicate that thyroid function also influences the degradation of insulin in man (41). An increased rate of insulin degradation without a comparable increase in the rate of insulin production in the thyrotoxic patient would result in subnormal amounts of available insulin and a decreased rate of glucose utilization.…”

“…A negative C eq value is theoretically due to increased peripheral glucose utilization or decreased net hepatic glucose output, or both. There is evidence that, following administration of insulin, peripheral glucose utilization is not increased (or actually decreased) in some patients with liver disease (41) and hypothyroidism. It is therefore probable that the negative C eq values in these two groups of patients were due largely to a decreased net hepatic output of glucose without an increase (or with an actual decrease) in peripheral glucose utilization.…”

The Physiologic Significance of the Secretion of Endogenous Insulin Into the Portal Circulation. I. Comparison of the Effects of Glucagon-Free Insulin Administered via the Portal Vein and via a Peripheral Vein on the Magnitude of Hypoglycemia and Peripheral Glucose Utilization1

“…Arteriovenous glucose differences were not measured, and the studies were concerned primarily with the hyperglycemic effect of insulin (18,19) (6,24). For these reasons the effects obtained with insulin known to contain glucagon are not comparable to those obtained with glucagon-free insulin.…”

Endocrinology

“…The liver, kidney, and muscle are likely to be especially important sites of glucagon degradation, although many tissues concentrate glucagon. Elrick et al (489 ) have presented further evidence that glucagon may work synergistically with insulin in enhancing the peripheral utilization of glucose, although their effects on the liver and blood glucose appear to be antagonistic (490). Lazarus et al (491) have shown that in rabbits pretreated with cortisone there is a marked initial rise in blood sugar following a large intravenous dose of commercial insulin.…”