Whether insulin acts immediately on the liver to reduce its rate of glucose output is a matter of great current interest. From the theoretical aspect, the answer given to this question has serious implications with respect to hypotheses concerning the mechanism of insulin action. In particular, an increase in permeability to glucose of the hepatic cell membrane should increase rather than decrease its rate of glucose output. In the hepatic cell, in contrast to the muscle cell, the net flow of glucose is from inside to outside the cell, and an increased facility for glucose transport across the cell membrane of the kind postulated for insulin action on the muscle cell could serve only to increase this flow and not to decrease it.Several investigative groups have used C14 glucose in attempts to supply the answer to this question, and the divergent findings that have resulted have been summarized and evaluated in a recent article.' In the present communication special consideration is given to the extent to which these divergencies are due, on the one hand, to diflerences in experimental findings brought about by dserences in experimental conditions and procedures, and are due, on the other hand, to differences in interpretation and calculation.
Glucose uniformly labeled with C14 was administered intravenously in minute amounts to unanesthetized dogs in the postabsorptive state as an initial dose followed by a continuous infusion. The C14 content of the plasma glucose was determined at intervals. When the ratio of priming dose to infusion rate was suitable, the plasma glucose specific activity remained relatively constant during the 60–180-minute period of the infusion, whereas during the first 60 minutes it decreased in a manner indicating the presence of two compartments exchanging glucose with the plasma glucose compartment. For a typical experiment of this kind, the amounts of glucose in these compartments and the rates at which these bodies of glucose underwent mixing with the plasma glucose were calculated. It was then possible to determine the magnitude of the errors in body glucose pool size and inflow-outflow (i.e., turnover) rate which are made when measurements are carried out at various ratios of priming dose to infusion rate. These errors are incurred when the usual simplifying assumption is made that instantaneous mixing occurs throughout the body glucose pool. It was found that there is an extensive range of ratios of initial dose to infusion rate over which the errors are small enough (less than ± 5%) to be ignored; it is not necessary to carry out a preliminary experiment on each dog to establish a desirable ratio. Average values of body glucose pool size and glucose inflow-outflow rate obtained in 10 experiments with seven normal dogs are compared with values which have been reported by others. The physiological significance of these parameters measured by isotope dilution is discussed.
C14 glucose was adminisered continuously to unanesthetized normal dogs by intravenous infusion following a priming dose at a rate which maintained the specific activity of the circulating glucose at a nearly constant level. Glucagon-free insulin was then administered intravenously in varying doses. Samples of blood were collected at intervals throughout the experiment and more frequently just subsequent to insulin injection. The glucose concentration of the circulating blood and the specific activity of this glucose, when considered together, allow calculations to be made of a) the outflow of glucose toward the tissue cells, and b) the inflow of glucose from the liver during the period after insulin injection. By this means it was shown that increased glucose uptake by the tissues is much more important than decreased delivery of glucose by the liver in bringing about insulin-induced hypoglycemia. It was also shown that recovery from hypoglycemia is brought about by increased glucose delivery by the liver and not by a decrease in tissue uptake of glucose below the preinsulin level. Alternative methods of calculation of absolute values for glucose inflow and outflow during periods of changing blood glucose concentrations are discussed and evaluated.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.