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

Abstract

In recent years much interest has been focused on the plasma level of nonesterified fatty acid (NEFA), or unesterified fatty acid (UFA), and on its role as an energy substrate, particularly for muscle and liver.Both insulin and glucose produce a rapid fall in serum NEFA level (1, 2), which is related to a decreased output of NEFA from the adipose cell (3, 4). The concept has arisen that in the fasting state NEFA is continuously mobilized from fat stores, and when glucose becomes available, this mobilization ceases and the blood level falls (5).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. METHODSStudies have been carried out on six normal fasting human subjects. Indwelling Cournand needles were placed in one femoral artery and in both femoral veins under procaine anesthesia. Simultaneous control samples were drawn from each of these three sites, followed by a small dose of glucagon-free insulin (one-half to one unit) injected intra-arterially. Thus insulin was injected directly into one limb, reaching the other limb after at least one circuit and in smaller concentration.Care was taken to insure simultaneous withdrawal of

Effect of Intra-arterial Insulin on Tissue Cholesterol and Fatty Acids in Alloxan-Diabetic Dogs

“…15 -10 In normal man, it was recently demonstrated that intra-arterial administration of insulin caused a significant decrease of the arterial concentration and the arteriovenous difference of the nonesterified fatty acids. 17 This result is interpreted as indication of a local effect of the insulin on the tissues of the injected leg, causing a decrease in the release of nonesterified fatty acids to the venous blood.…”

Effect of glucose load and of insulin on the metabolism of glucose and of palmitate in sheep

“…The work discussed below indicates that this was due to the effect of glucose on the adipose tissues of the sheep. Gordon (1957) has shown that in starved human subjects arterial and saphenousvein samples reveal large negative arteriovenous differences, which indicate a net release of fatty acid from adipose tissue and which are abolished by the administration of glucose or insulin (Gordon, 1957;Estes, Bogdonoff, Freidberg, Harlan & Trout, 1959). Experiments in vitro, mainly with the epididymal fat pads of rats, have shown that glucose strongly stimulates the incorporation of [14C] glucose into glyceride glycerol and fatty acids (Lynn, MacLeod & Brown, 1960;Cahill, Leboeuf & Flinn, 1960;Jeanrenaud & Renold, 1959;Winegrad, Shaw, Lukens, Stadie & Renold, 1959).…”

Role of Free Fatty Acids in Forearm Metabolism in Man, Quantitated by Use of Insulin*

“…There have been a number of reports on effects of insulin on plasma FFA concentrations and on arteriovenous FFA concentration differences (4,5,16,17). In most instances insulin was given intravenously, but even when administered intraarterially, the dose was usually so large-usually 1 U or greater-that the effect was like that of an intravenous dose.…”

“…Insulin-induced inhibition of FFA release has, however, been unequivocally shown across the femoral arterial-saphenous venous drainage bed (4,5) (18).…”