The 1987 Upjohn award lecture. The role of membrane transport in the control of glucose metabolism and its coupling to cellular function.
In muscle and some other tissues the membrane transport of glucose is normally rate limiting for glucose utilization. It is modulated by insulin, muscular contraction, availability of oxygen and alternative substrates, and many other factors. An increase in glucose transport is associated with interventions increasing the influx of Ca2+ or its release from internal stores, thus presumably raising cytoplasmic [Ca2+]. Recent results with isolated myocytes from adult rat hearts are shown to be consistent with this hypothesis, and supporting evidence was obtained with other cell types. In avian erythrocytes glucose transport was found to be modulated only by internal Ca2+ redistribution, as plasmalemmal fluxes were very slow. In isolated bovine adrenal chromaffin cells glucose transport was found to be increased in a Ca2+-dependent manner by insulin (resembling muscle) and by stimulators of catecholamine secretion. These features are essentially preserved during the morphologic changes these cells undergo when cultured. Thus, enhanced glucose transport is often coupled to increased energy production for contraction, secretion, growth, etc., and to some hormonal signals. Other factors, notably the oxidation of fatty acids, exert a suppressive influence; this negative feedback may account in part for the decreased peripheral response to insulin in diabetes. It is suggested that binding of Ca2+ to a regulatory site, perhaps involved in the translocation of glucose transporters to the plasma membrane, may be involved in these regulatory phenomena and may play a central role in coupling glucose transport to a variety of other cellular processes.
D000818:Animals; D001693:Biological Transport, Active; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D008954:Models, Biological; D009119:Muscle Contraction; D010042:Ouabain / Q000494:pharmacology
D000001:Calcimycin; D010042:Ouabain; D005947:Glucose; D002118:Calcium; D004837:Epinephrine