Effect on Femoral a-v Glucose Difference of Insulin Injected Into an Antecubital Vein and Into a Femoral Artery 1

Abstract

There still exists considerable controversy with respect to the importance of the liver as compared to the peripheral tissues (skeletal muscle) in the homeostasis of blood sugar levels. The place and mechanism of action of insulin remain unclear.Mann and Magath (1) are credited with first establishing the peripheral action of insulin apart from the liver. This was done in evisceration experiments in dogs. Frank, Nothmann and Wagner (2, 3), working with rabbits and pancreatectomized dogs, claimed a local peripheral action of insulin following its injection into a femoral artery. In vitro, it has been shown that the glucose uptake of the rat diaphragm is increased under the action of added insulin (4-6). Stadie and Zapp (7) have demonstrated that insulin is fixed to the diaphragm and cannot be washed off.The purpose of this paper is to record data demonstrating the different effect on femoral A-V glucose difference of insulin injected into a femoral artery and into an antecubital vein. METHODSConvalescent hospital patients and normal medical students served as subjects.All studies were done in the morning and the subjects had had no food for 12 to 14 hours. They were at rest for an hour prior to insulin injection. No attempt was made to control room temperature.The main femoral artery and vein were used for sampling. Samples were drawn simultaneously into heparinized syringes and immediately transferred to tubes prepared by the evaporation of 1 ml. of 3 percent sodium fluoride and these were then placed in ice. Using barium hydroxide and zinc sulfate precipitation, filtrates were made at the completion of the experiment.

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

“…Although the time of exposure of the liver to this larger amount of insulin is only a few seconds, i.e., the duration of a single circulation through the liver, other data indicate that exposure of an extremity to a large amount of insulin for a similar duration of time also augments the metabolic response of that limb (17). Bell and Burns showed that the intraarterial injection of insulin resulted in a significantly greater A-V glucose difference in the injected leg compared to the contralateral extremity (17).…”

“…Although the time of exposure of the liver to this larger amount of insulin is only a few seconds, i.e., the duration of a single circulation through the liver, other data indicate that exposure of an extremity to a large amount of insulin for a similar duration of time also augments the metabolic response of that limb (17). Bell and Burns showed that the intraarterial injection of insulin resulted in a significantly greater A-V glucose difference in the injected leg compared to the contralateral extremity (17). In the intact animal, after the intravenous injection of insulin, the magnitude of the metabolic response of a tissue sensitive to insulin would be expected to depend, not only upon the affinity of the tissue for insulin, but also upon the per cent of the cardiac output perfusing the tissue per unit time, i.e., on the delivery of insulin to the tissue.…”

Studies on the Physiology of Hunger. I. The Effect of Intravenous Administration of Glucose on Gastric Hunger Contractions in Man 1

“…Studies of carbohydrate metabolism have long utilized peripheral arteriovenous glucose differences, q their equivalent, capillary-venous differences - (9,11,(17)(18)(19). In the presence of a constant blood flow,4 such differences depend upon the rate at which glucose is removed by the tissues, and these removal rates are closely related to the general level of carbohydrate stores.…”

“…On one matter there has been unanimity: all reports have agreed that glucose abolishes gastric hunger contractions which have been induced by insulin hypoglycemia (4-6, 26, 27). Since insulin administration presumably increases the rate at which glucose is utilized (18,28), this observation suggests that it is the utilization rate which determines the effect of intravenous glucose on gastric motility. None of these studies, however, reported an attempt to measure such utilization.…”

The Effect of Insulin on Nonesterified Fatty Acid Release From the Human Leg*

“…Several years ago Bell and Burns (6) showed that the intra-arterial injection of small doses of insulin into the leg of a human subject caused a prompt widening of the arteriovenous (A-V) difference for glucose across the injected limb as compared to the opposite noninjected limb. This apparent fixation of the insulin in the injected limb and the resulting differential metabolic effect seemed to offer an opportunity to study further the effect of insulin on NEFA handling by the peripheral tissues.…”