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J E Foley

Publications and source records attributed to J E Foley.

At least 109 records · Page 6Linked to original sources
PubMed1981

Accumulation of 2-deoxyglucose against its concentration gradient in rat adipocytes.

Rat adipocytes were incubated at 37 degrees C with 2-deoxy-D-[1-14C]glucose ([14C]2dGlc) at various concentrations and the intracellular concentrations of [14C]2dGlc and deoxy[14C]glucose phosphate ([14C]2dGlcP) were measured. Using 7 microM extracellular [14C]2dGlc, the intracellular [14C]2dGlc concentration approached the extra-cellular by 5 min insulin-stimulated cells and by 60 min it exceeded the extracellular concentration by 50-fold. A maximum accumulation ratio of 3.5 was reached by 7 min using 1 mM and a ratio of 1.6 was reached by 1 to 3 min using 10 mM extracellular 2dGlc. The time at which the concentration of intracellular 2dGlc exceeded the extracellular was inversely related to the accumulation of 2dGlcP. The rate of accumulation of total radioactivity ([14C]2dGlc plus [14C]2dGlcP) decreased after 20 min using 7 microM extracellular [14C]2dGlc. This change occurred later at 22 degrees C or in the absence of insulin and sooner at higher concentrations of 2dGlc. Experiments where uptake was stopped by dilution indicated that radioactivity appearing in the medium was [14C]2dGlc, but radio-activity disappearing from the cells was largely [14C]2dGlcP. Addition of 10 mM unlabelled 2dGlc or glucose to cells preincubated with 7 microM [14C]2dGlc resulted in a more rapid loss of accumulated label from the cells, while addition of 10 mM 3-O-methylglucose, a non-metabolizeable sugar analogue with about the same affinity for the transport system as 2dGlc, was without effect. The results show that 2dGlc is accumulated against its concentration gradient. It is suggested that the mechanism involves first, dephosphorylation of 2dGlcP and second, the presence of a diffusion barrier between the site of dephosphorylation and the transport site.

Adipose Tissue↗
PubMed1981

Termination of insulin-induced hexose transport in adipocytes.

The hexose transport of insulin-pretreated (80 pM) adipocytes remained elevated for at least 45 min when the cells were depleted of ATP by treatment with dinitrophenol. On the other hand, the half-time of deactivation of hexose transport in insulin-pretreated cells was of the same magnitude as that of dissociation of receptor-bound insulin both in the absence and presence of glucose (about 8 min). Thus, a high ATP-level, but not ongoing glucose metabolism appears to be important for termination of the insulin effect shortly after dissociation of insulin from its receptor.

Adenosine Triphosphate↗
PubMed1981

Effects of dietary composition on glucose metabolism in rat adipose cells.

The effect of altered dietary carbohydrate and fat content on equilibrium insulin binding to, and glucose transport activity and metabolism in, isolated rat epididymal adipose cells has been studied. Alterations in basal and insulin-stimulated total glucose utilization induced by changes in the ratio of dietary carbohydrate to fat are accounted for by specific effects of dietary composition at two levels of cellular function: 1) glucose transport across the cell's plasma membrane, specifically, the number of functional glucose transport systems, and 2) the cell's maximal capacity for glucose metabolism. These effects occur without alterations in insulin binding or the cell's sensitivity to insulin. Furthermore, diet-induced changes in the pattern of 14CO2, and 14C-triglyceride glycerol and fatty acid production appear to be accounted for primarily by the influence of dietary composition on the total amount of glucose entering the cell. Thus, under the conditions of this study, changes in dietary composition alter the adipose cell's capacities for glucose transport and metabolism without altering the mechanisms of insulin action or regulating the metabolic flow of glucose carbons.

Adipose Tissue↗
PubMed1981

Glucose transport in isolated rat adipose cells.

Several different approaches to the measurement of hexose transport rates in isolated adipocytes from lean and obese rats have been utilized in the last six years. The uptake as a function of time of the non-metabolizable sugar 3-0-methylglucose is so fast that until recently no measurements of the 'true' transport rates (ie initial velocity of influx) could be made. Other nonmetabolizable sugars such as L-arabinose are taken up more slowly, due to their low affinities and their influxes at early times are measureable. Alternatively, the uptake with time of 2-deoxyglucose, an analogue of glucose which is transported and phosphorylated, but not further metabolized, has been used extensively as a measure of transport rate. The data from different studies comparing the transport rates in adipocytes from lean and obese rats are at variance. The present discussion is an attempt to explain why the results of such studies have not always agreed. In addition, as a result of our recent studies comparing 2-deoxyglucose and 3-0-methylglucose transport, we introduce a new model of hexose transport in adipocytes.

3-O-Methylglucose↗
PubMed1980

Glucose-induced acceleration of deoxyglucose transport in rat adipocytes. Evidence for a second barrier to sugar entry.

The transport of trace (a concentration much less than Km for transport) 2-deoxyglucose (deoxyglucose) and 3-O-methylglucose (methylglucose) into rat adipocytes was measured using 1- to 2-s pulses at 37 degrees C in the absence of glucose and in the presence of glucose with and without pre-exposure to glucose. Pre-exposure of insulin-stimulated adipocytes to 10 mM glucose for 30 min resulted in an acceleration of trace deoxyglucose transport above that seen in the absence of glucose. In contrast, when glucose was added together with deoxyglucose, an inhibition of transport was observed. There was no effect up to 5-min pre-exposure to 10 mM glucose, but acceleration appeared thereafter and reached a steady state by 30 min, i.e. a 3-fold higher transport rate than that seen when deoxyglucose and glucose were added together. Glucose (3.5 mM) appears to be a threshold concentration for this effect. A smaller effect was seen in the absence of insulin (1.5-fold) using 10 mM glucose and in the presence of insulin using 10 mM mannose (2.7-fold). No effect was seen using 10 mM galactose, fructose, pyruvate-lactate, deoxyglucose, and methylglucose. There was no effect of glucose pre-exposure on insulin-stimulated methylglucose transport. We propose that entry occurs across two independent barriers in series separated by an aqueous pore, that transport across the second barrier is more rate limiting for deoxyglucose than for methylglucose, and than metabolites of glucose decrease the resistance of the second barrier to deoxyglucose transport.

Adipose Tissue↗
PubMed1980

Insulin binding and hexose transport in rat adipocytes. Relation to cell size.

Insulin binding, initial velocity of [14C]methylglucose transport, uptake of [14C]deoxyglucose and conversion of [U-14C]glucose to CO2, glyceride-glycerol and fatty acids were measured at 37 degrees C in adipocytes from rats of different weights (135-450 g) and therefore with different mean cell volumes (53-389 pl). Insulin binding per cell increased with increasing cell size and binding was 2.3 times higher in the largest cells than in the smallest cells with tracer alone. The difference was largely accounted for by an increase in the apparent affinity. Influx of methylglucose per cell increased with increasing cell size in the absence of insulin and remained constant as a function of cell size in its presence. The effect of insulin ranged from 11 fold in small cells to 3.5 fold in large cells. The rat of conversion of [U-14C]glucose to CO2 and lipids was about half of the rate of methylglucose transport under all conditions. In contrast, the uptake of deoxyglucose in insulin-stimulated cells decreased markedly with increasing cell size. Increasing cell size caused a small decrease in sensitivity which could be explained by a smaller amont of insulin bound per unit surface area. The results show that increasing cell size/animal weight causes changes in insulin binding which may explain changes in sensitivity. In addition, the hexose transport system is modified in a way which is not explained by changes in insulin binding. Finally, changes in deoxyglucose uptake with cell size do not parallel changes in methylglucose transport.

Adipose Tissue↗
PubMed1980

Rate-limiting steps of 2-deoxyglucose uptake in rat adipocytes.

2-Deoxy[1-14C]glucose uptake in rat adipocytes was measured as a function of time in the absence and presence of unlabelled glucose or 2-deoxyglucose. Uptake of tracer alone was linear from 2s to 6 min. At 37 degrees C the rate of uptake in insulin-stimulated cells decreased markedly after a few seconds in the preence of glucose (0.5-10 mM) and after 0.5-2 min in the presence of deoxyglucose (2-10 mM). Similar data were obtained at 22 degrees C. With 10 mM glucose (37 degrees C, 30 s) approx. 80% of the intracellular radioactivity was non-phosphorylated deoxyglucose and with 10 mM deoxyglucose approx. 40% was non-phosphorylated. The results show that deoxy[14C]glucose uptake after a few minutes is mainly limited by hexokinase in the presence of glucose and at least partially in the presence of deoxyglucose. The data suggest caution in using deoxyglucose uptake as a measure of transport, especially in complex kinetic studies. In addition, the initial velocity of tracer * 3-O-methylglucose was found to be approx. 2-fold higher than that of tracer deoxyglucose even though both sugars inhibited the initial velocity of labelled methylglucose half-maximally at a concentration of 5 mM. These data suggest a fundamental difference between deoxyglucose and methylglucose transport.

Adipose Tissue↗
PubMed1980

Intracellular glucose concentration in small and large rat adipose cells.

Intracellular free glucose concentrations have been estimated in small and large isolated epididymal adipose cells prepared from young lean and older obese rats using glucose-induced steady-state tracer 3-O-methylglucose countertransport. Steady-state 3-O-methylglucose uptake was measured in the presence of 2--50 mM glucose or sucrose in the absence or presence of 100 microU insulin/ml. The ratio of the uptake of 3-O-methylglucose in the presence of glucose to that in the presence of sucrose at each sugar concentration was then utilized to estimate the corresponding intracellular glucose concentration. At all three extracellular glucose concentrations tested in the absence of insulin, intracellular concentrations of glucose are greater in the large cells than in the small cells. In the presence of 2 mM glucose and insulin, on the other hand, intracellular glucose concentrations of 2 mM are attained, regardless of cell size. These results suggest that transport may not be the rate-limiting step for glucose metabolism at physiologic glucose concentrations either in the enlarged adipose cell in the absence or presence of insulin or in the small adipose cell in the presence of maximally stimulating concentrations of insulin.

Adipose Tissue↗
PubMed1979

Effect of beta-blockers on exercise double product (systolic blood pressure x heart rate).

1 The effect of single oral doses of six beta-receptor antagonists on exercise-induced changes in double product (systolic blood pressure x heart rate) were studied in 25 human volunteers. 2 Three doses of propranolol, nadolol, oxprenolol, pindolol, timolol and atenolol were selected for study on the basis of in vivo beta-blocking potency. 3 Although all beta-blockers studied reduced the double product response to exercise, the pharmacodynamics of this effect differed markedly. 4 Pharmacodynamic half-lives, estimated for the drug tested, were 39 h for nadolol, atenolol 21 h, timolol 15 h, oxprenolol 13 h, propranolol 11 and pindolol 8 h. 5 These results suggest that the clinical choice of a beta-blocker with the least problems of compliance can be made on the basis of pharmacodynamics as well as pharmacological profile.

Adolescent↗
PubMed1978

Glucose transport in isolated rat adipocytes with measurements of L-arabinose uptake.

Data is presented suggesting that rates of L-arabinose transport, calculated from L-[1-14C]arabinose uptake measurements, can be used as indicators of changes in the rates of glucose transport in isolated rat adipocytes. L-[1-14C]arabinose, at 37 degrees C, was found to be nonmetabolizable and taken up by adipocytes exponentially with time reaching 95% of equilibrium in 30 min. When L-arabinose is corrected for background, the corrected uptake values conform to the time-dependent monoexponential uptake relationshiop predicted for a facilitated transport system and are not significantly different from 0 in the presence of 70 micron cytochalasin B. Transport rates were calculated from corrected uptake values near the half-maximal uptake of L-arabinose and from a value of the total amount of L-arabinose in the cell at equilibrium. Competitive inhibition of L-arabinose transport by glucose and countertransport of L-arabinose in the presence of glucose suggest that L-arabinose and glucose share the same transport system. Data is presented demonstrating the effect of insulin and dexamethasone on the transport system that confirms the conclusions obtained by other investigators using other methods.

Adipose Tissue↗
PubMed1978

A concept for the control of kidney production of erythropoietin involving prostaglandins and cyclic nucleotides.

Our hypothesis is that PGs released within the kidney play a role in the modulation of kidney production of Ep. PGs release probably at medullary and/or cortical sites following erythropoietic stimuli such as hypoxic hypoxia, anemic hypoxia, and ischemic hypoxia induced by renal artery constriction increase kidney production of Ep. PGs which are released probably activate a renal cortical adenylate cyclase thereby enhancing the production of intracellular cAMP. This initiates the cascade of events resulting in the production and/or secretion of Ep by the kidney. The endoperoxide analogs and PGE2 have been found to produce a dose-related and Ep-dependent increase in radioiron incorporation into newly formed red blood cells of exhypoxic polycythemic mice. Indomethacin, a potent PG cyclo-oxygenase inhibitior, attenuates Ep production and the appearance of PGE in the renal venous effluent of animals exposed to hypoxic hypoxia and renal artery constriction. Arachidonic acid (C20:4) and PGE2 infusion into the posthypoxic isolated perfused dog kidney produced a significant elevation in Ep titers in the perfusate. The increase in Ep production caused by arachidonate is blocked by indomethacin. It has been previously reported that PGs of the E series stimulate cAMP formation in several tissues. We have found that not only are renal cortical cAMP levels significantly elevated in rats following exposure to hypobaric hypoxia but that dibutyryl cAMP administration produces an increase in hematocrit and circulating red cell mass in normal mice. Our data thus far strongly support the hypothesis that the renal PGs and the cyclic nucleotides are intimately involved in the pharmacologic and/or pathophysiologic control of Ep production. Further work is necessary to determine whether the PGs and cyclic nucleotides are involved in the day-to-day control of Ep production by the mammalian kidney.

Animals↗
PubMed1978

The effects of arachidonic acid on erythropoietin production in exhypoxic polycythemic mice and the isolated perfused canine kidney.

The ability of arachidonic acid (AA), the bisenoic prostaglandin precursor to stimulate erythropoiesis and erythropoietin (Ep) production in exhypoxic polycythemic mice and the programmed isolated perfused canine kidney was investigated. Arachidonate in the lowest dose tested (50 microgram/kg i.p.) maximally stimulated erythropoiesis when administered to exhypoxic polycythemic mice. Kidneys from dogs made hypoxic for 4 hr at 0.42 atm pressure were perfused (2--3 ml/g/min, 37 degrees C) in a closed circuit system for 5 hr with blood from nonhypoxic donors. AA infusion (80 microgram/min) caused a significant (P less than .05) increase in erythropoietic activity of the perfusate as measured by the percentage of 48-hr 59Fe incorporation into red blood cells of exhypoxic polycythemic mice per milliliter of perfusate from an initial value of 1.66 +/- 0.50% to 6.05 +/- 0.96% over the 1st hr of infusion whereas vehicle controls showed no change. To determine whether this increase in Ep production was dependent on biosynthesis of renal prostaglandins and their intermediates, the ability of indomethacin to block AA-induced Ep production was studied. When kidney donors were twice pretreated with indomethacin 12 hr and immediately before their hypoxic exposure, no increase in Ep titers were seen during AA infusion. These results support the hypothesis that endogenously synthesized prostaglandins, their intermediates and/or other products of AA metabolism, such as prostacyclin and prostaglandins play an important role in the control Ep production.

Animals↗