Exogenous Glucose Uptake Research Articles

ANKRD22 is a potential novel target for reversing the immunosuppressive effects of PMN-MDSCs in ovarian cancer

BackgroundOvarian cancer is the deadliest type of malignant gynecological tumor. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are involved ovarian cancer and are closely related to adverse outcomes. However, the immunosuppressive mechanism...

Glucose clearance and uptake is increased in the SOD1G93A mouse model of amyotrophic lateral sclerosis through an insulin-independent mechanism.

Metabolic disturbances are associated with the progression of the neurodegenerative disorder, amyotrophic lateral sclerosis (ALS). However, the molecular events that drive energy imbalances in ALS are not completely understood. In this study, we aimed to elucidate deficits in energy homeostasis in the SOD1G93A mouse model of ALS. SOD1G93A mice and their wild-type littermates underwent indirect calorimetry and intraperitoneal glucose/insulin tolerance tests at both the onset and mid-symptomatic stages of the disease. Glucose uptake and the plasma glucoregulatory hormone profiles were analyzed. Pancreatic islet cell mass and function were assessed by measuring hormone concentrations and secretion in isolated islets, and pancreatic α- and β-cell immunoreactive areas. Finally, we profiled liver glycogen metabolism by measuring glucagon concentrations and liver metabolic gene expressions. We identified that mid-symptomatic SOD1G93A mice have increased oxygen consumption and faster exogenous glucose uptake, despite presenting with normal insulin tolerance. The capacity for pancreatic islets to secrete insulin appears intact, however, islet cell insulin concentrations and β-cell mass were reduced. Fasting glucose homeostasis was also disturbed, along with increased liver glycogen stores, despite elevated circulating glucagon, suggesting that glucagon signaling is impaired. Metabolic gene expression profiling of livers indicated that glucose cannot be utilized efficiently in SOD1G93A mice. Overall, we demonstrate that glucose homeostasis and uptake are altered in SOD1G93A mice, which is linked to an increase in insulin-independent glucose uptake, and a loss of β-cells, insulin production, and glucagon sensitivity. This suggests that the hormonal regulation of glucose concentrations may contribute to the progression of disease in this ALS mouse model.

Glucose metabolism and metabolic flexibility in blood platelets

Essentials The metabolic integration processes required for platelet activation are unclear. The metabolic plasticity of human platelets were investigated. Activated platelets exhibit a glycolytic phenotype while preserving mitochondrial function. Platelets can switch freely between glucose/glycogen and fatty acids to support aggregation. SUMMARY: Background Platelet activation is an energy-dependent process, but the type and integrated use of metabolic fuels required to drive activation remain unclear. Objective To dissect the metabolic fuel and pathway plasticity required for platelet activation. Methods Platelet oxygen consumption rate and extracellular acidification rate were measured as markers of oxidative phosphorylation (OXPHOS) and glycolysis, respectively. Glucose and glycogen were quantified by enzyme-coupled fluorometric assay. Results Blood platelets switched freely between glycolysis and OXPHOS, using either glucose or fatty acids at rest. The transition of platelets from a quiescent to an activated state promoted rapid uptake of exogenous glucose, associated with a shift to a predominantly glycolytic phenotype coupled with a minor rise in mitochondrial oxygen consumption. Consistent with this metabolic plasticity, under nutrient-limiting conditions, platelets utilized glucose, glycogen or fatty acids independently to support activation. Importantly, the glycolytic switch occurred even in the absence of extracellular glucose, originating from endogenous glycogen. Focusing on the relative flexibility of mitochondrial fuel oxidation of glucose and fatty acids, we found that inhibition of oxidation of a single fuel was compensated for by increased oxidation of the other, but, when oxidation was inhibited, glycolysis was upregulated. Glutamine made little contribution to mitochondrial oxygen consumption. Analysis of platelet functional dependency on ATP from different pathways demonstrated that inhibition of both fuel oxidation and glycolysis were required to prevent agonist-driven platelet activation. Conclusion Platelets have significant metabolic fuel and pathway flexibility, but preferentially use glycolysis for ATP generation when activated.

Exogenous glucose oxidation is reduced with carbohydrate feeding during exercise after starvation

Lean healthy individuals are characterized by the ability to rapidly adapt metabolism to acute changes in substrate availability and metabolic rate. However, in glucose-intolerance/insulin-resistant conditions, such as that induced by starvation, the flexibility of tissues to rapidly respond to change in substrate availability is diminished. We asked whether the conundrum of increased glucose demand by the contracting skeletal muscle during prolonged exercise and the glucose intolerance of starvation would result in the obstruction of oxidative disposal of ingested 13C-labeled glucose during exercise. Seven lean, healthy, physically active individuals (2 women, 5 men) completed a randomized crossover study comparing the effects of the normal-fed condition vs a 67-hour water-only fast on the metabolic response to carbohydrate ingestion during 80 minutes of exercise at 56% of maximum oxygen uptake. Compared with the normal condition, fasting resulted in a large overall increase in the rate of fat oxidation (mean effect, 71%; 95% confidence limit, ±22%) and moderate reductions in both exogenous (−54%, ±10%) and endogenous (−40%, ±19%) glucose oxidation rates during exercise. Over the course of exercise, fat oxidation was impermeable to change in the fasting condition, but increased moderately (33%, ±19%) in the normal condition. These changes were associated with a large increase in plasma free fatty-acid concentration (120%, ±64%) and a moderate increase in blood lactate concentration (58%, ±50%). In contrast, large reductions in resting blood glucose (−21%, ±14%) and moderate reductions in plasma insulin concentrations (−47%, ±26%) were observed in the fast condition; but this effect was reversed for glucose (30%, ± 24%) and negated for insulin by the end of exercise. To conclude, a 67-hour fast leads to an impermeable increase in fat oxidation, suppression of both exogenous and endogenous carbohydrate oxidation, and a metabolic response consistent with resistance to contraction-induced exogenous glucose uptake and oxidation.

Exenatide Sensitizes Insulin-Mediated Whole-Body Glucose Disposal and Promotes Uptake of Exogenous Glucose by the Liver

OBJECTIVE— Recent progress suggests that exenatide, a mimetic of glucagon-like peptide-1 (GLP-1), might lower glycemia independent of increased β-cell response or reduced gastrointestinal motility. We aimed to investigate whether exenatide stimulates glucose turnover directly in insulin-responsive tissues dependent or independent of insulinemia.RESEARCH DESIGN AND METHODS— An intraportal glucose infusion clamp was used in dogs to measure glucose turnover to encompass potent activation of the putative glucose/GLP-1 sensor in the porto-hepatic circulation with exenatide. The modified glucose clamp was performed in the presence of postprandial hyperinsulinemia and hyperglycemia with exenatide (20 μg) or saline injected at 0 min. Furthermore, the role of hyperglycemia versus hyperinsulinemia in exenatide-mediated glucose disposal was studied.RESULTS— With hyperinsulinemia and hyperglycemia, exenatide produced a significant increase in total glucose turnover by ∼30%, as indicated by portal glucose infusion rate (saline 15.9 ± 1.6 vs. exenatide 20.4 ± 2.1 mg · kg−1 · min−1, P < 0.001), resulting from increased whole-body glucose disposal (Rd, ∼20%) and increased net hepatic uptake of exogenous glucose (∼80%). Reducing systemic hyperglycemia to euglycemia, exenatide still increased total glucose turnover by ∼20% (saline 13.2 ± 1.9 vs. exenatide 15.6 ± 2.1 mg · kg−1 · min−1, P < 0.05) in the presence of hyperinsulinemia, accompanied by smaller increments in Rd (12%) and net hepatic uptake of exogenous glucose (45%). In contrast, reducing hyperinsulinemia to basal levels, exenatide-increased total glucose turnover was completely abolished despite hyperglycemia (saline 2.9 ± 0.6 vs. exenatide 2.3 ± 0.3 mg · kg−1 · min−1, P = 0.29).CONCLUSIONS— Exenatide directly stimulates glucose turnover by enhancing insulin-mediated whole-body glucose disposal and increasing hepatic uptake of exogenous glucose, contributing to its overall action to lower postprandial glucose excursions.

Fructose-2,6-bisphosphate, a potent stimulator of phosphofructokinase, is increased by high exogenous glucose perfusion.

We have previously demonstrated that perfusion of isolated hearts with high concentrations of glucose results in increased glycolysis during ischemia, diminished ischemic injury, and improved functional recovery with reperfusion. To evaluate a possible mechanism by which glucose conferred this protection. We examined the hypothesis that increased exogenous glucose concentrations results in increased concentrations of fructose-2,6-bisphosphate, a potent activator of phosphofructokinase-1, and thus increases glycolysis. Perfused rabbit hearts were subjected to 60 min of low-flow ischemia. Control hearts were perfused with buffer containing 0.4 mmol/l palmitate, 5 mmol/l glucose, and 70 mU/l insulin, and treated hearts were perfused with buffer containing 0.4 mmol/l palmitate, 15 mmol/l glucose and 210 mU/l insulin. Ischemic contracture was attenuated by perfusion of high concentrations of glucose (high glucose) (P < 0.05 compared with control). Glucose uptake and lactate production were greater in hearts perfused with high glucose, as was the ATP concentration at the end of ischemia (P < 0.05 compared with controls). Exogenous glucose uptake and lactate production correlated well with fructose-2,6-bisphosphate content (P = 0.007). Enhancement of glycolysis in hearts perfused with high glucose may be the result of stimulation of phosphofructokinase-1 by fructose-2,6-bisphosphate. Accordingly, this may serve as an important mechanism by which cardioprotection may be achieved.

Maximal parenteral glucose oxidation in hypermetabolic young children: a stable isotope study.

During periods in which nutrition support of critically ill young children must be parenteral, glucose infusions are administered at up to 10 or more mg.kg-1.min-1 to meet predicted energy needs. However, data in adults suggest that such high glucose loads exceed the ability to oxidize glucose in the hormonal milieu that characterizes critical illness. The purpose of this study was to determine if these high glucose loads are oxidized by critically ill young children. Ten young children with serious burns were enrolled in a stable isotope study of glucose metabolism. These five boys and five girls were an average age of 5.2 years (range, 1 to 11 years), weight of 18.4 kg (range, 10 to 31 kg) and burn size of 51.6% of the body surface (range, 35% to 86%). During clinically required episodes of parenteral nutrition support, we used the [13C6]glucose tracer to assess the efficacy of glucose oxidation at both 5 and 8 mg.kg-1.min-1. Serum glucose was recorded and indirect calorimetry was performed. The fraction of exogenous glucose oxidation fell from 59% +/- 5% to 47% +/- 5% (p < .05). Although there was a significantly increased level of total glucose oxidation (3.2 to 3.8 mg.kg-1.min-1), this increment (29% +/- 9%) was accompanied by a significant decrease in the efficiency of energy production, because the bulk of the additional glucose above 5 mg.kg-1.min-1 was not being oxidized. Plasma glucose concentration did not change (145 +/- 4 vs 137 +/- 4 mg/dL, p < .01) and whole-body expired gas respiratory quotients remained consistent with a mixed fuel oxidation, implying that there exists an increased rate of exogenous glucose uptake by tissues in nonoxidative pathways. Maximum glucose oxidation in severely burned children occurs at intakes approximating 5 mg.kg-1.min-1. Exogenous glucose in excess of this amount enters nonoxidative pathways and is unlikely to improve energy balance. Clinical markers such as serum glucose levels or expired respiratory quotient may not detect inefficient glucose utilization.

Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart. A three tracer study of glycolysis, glycogen metabolism, and glucose oxidation.

Myocardial glucose use is regulated by competing substrates and hormonal influences. However, the interactions of these effectors on the metabolism of exogenous glucose and glucose derived from endogenous glycogen are not completely understood. In order to determine changes in exogenous glucose uptake, glucose oxidation, and glycogen enrichment, hearts were perfused with glucose (5 mM) either alone, or glucose plus insulin (40 microU/ml), glucose plus acetoacetate (5 mM), or glucose plus insulin and acetoacetate, using a three tracer (3H, 14C, and 13C) technique. Insulin-stimulated glucose uptake and lactate production in the absence of acetoacetate, while acetoacetate inhibited the uptake of glucose and the oxidation of both exogenous glucose and endogenous carbohydrate. Depending on the metabolic conditions, the contribution of glycogen to carbohydrate metabolism varied from 20-60%. The addition of acetoacetate or insulin increased the incorporation of exogenous glucose into glycogen twofold, and the combination of the two had additive effects on the incorporation of glucose into glycogen. In contrast, the glycogen content was similar for the three groups. The increased incorporation of glucose in glycogen without a significant change in the glycogen content in hearts perfused with glucose, acetoacetate, and insulin suggests increased glycogen turnover. We conclude that insulin and acetoacetate regulate the incorporation of glucose into glycogen as well as the relative contributions of exogenous glucose and endogenous carbohydrate to myocardial energy metabolism by different mechanisms.

713-6 Functional and Metabolic Protection of the Ischemic Rabbit Heart by NO Synthase Inhibitor

To assess the role of the NO pathway in ischemic injury, the NO synthase inhibitor L-N-Monomethylarginine (L-NMMA) was tested on isolated rabbit hearts retrogradely perfused with Krebs-Henseleit buffer containing 5.5 mM glucose and submitted to 30 min equilibration at 5 ml/min per g, followed by a 60 min low-flow ischemia (10% baseline) and 30 min reperfusion. Metabolic and physiological parameters of hearts treated with 1 μ M LNMMA added 15 min before ischemia (n = 10) were compared with similar parameters in controls (ctrl, n = 15) without the inhibitor. Before ischemia, L-NMMA did not influence left ventricular developed pressure or coronary perfusion pressure but lowered cyclic GMP by 25% (P = 0.01). During ischemia, L-NMMA decreased the severity of ischemic contracture (25 ± 3 vs 54 ± 4 mmHg in ctrl, P &lt; 0.001). Perfusion with D-NMMA did not protect the heart against ischemic contracture. The effect of L-NMMA was suppressed by 1 mM L-arginine or 10 μ M sodium nitroprussiate but not by 10 μ M 8Br- cyclic GMP. a cyclic GMP analogue. At the end of ischemia, exogenous glucose uptake was 0.90 ± 0.08 and 4.0 ± 0.2 μ mol/min per g DW (P &lt; 0.01). lactate production was 4.0 ± 0.7 and 8.0 ± 0.7 μ mol/min per g DW (P &lt; 0.01), glycogen was 15 ± 2 and 29 ± 5) μ mol glucose eqJg DW (P &lt; 0.01) and ATP was 2.5 ± 0.4 and 4.6 ± 0.3 μ mol/g DW (p &lt; 0.01) in ctrl and treated hearts, respectively. With reperfusion, the developed pressure was doubled (65 ± 5 vs 32 ± 3 mmHg, P &lt; 0.001) and the CPK release reduced by 50% (P &lt; 0.01) in hearts treated with L-NMMA vs ctrl. A dose-response curve of protection against ischemic damage by L-NMMA showed that the NO synthase inhibitor decreased ischemic contracture and enhanced glucose uptake between 1 nM and 1 μM, i.e. below concentrations inducing vasoconstriction. It is concluded that L-NMMA protects the ischemic rabbit heart against cellular damage by stimulating exogenous glucose uptake, thereby preserving endogenous energetic resources as glycogen. This protection during ischemia leads to an improvement of post-ischemic functional recovery. This effect during ischemia seems cGMP-independent.

Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium.

Even in the absence of a previous myocardial infarction, patients with coronary artery disease often present with chronic regional wall motion abnormalities that are reversible spontaneously or after coronary revascularization. In these patients, regional dysfunction has been proposed to result either from prolonged postischemic dysfunction (myocardial "stunning") or from adaptation to chronic hypoperfusion (myocardial "hibernation"). This study examines which of these two mechanisms is responsible for the chronic regional dysfunction often detected in patients with angina and noninfarcted collateral-dependent myocardium. Twenty-six anginal patients (19 men; mean age, 60 +/- 9 years old) with chronic occlusion of a major coronary artery but without previous infarction were studied. Positron emission tomography was performed to measure absolute regional myocardial blood flow with 13N-ammonia at rest (n = 26) and after intravenous dipyridamole (n = 11). The kinetics of 18F-deoxyglucose and 11C-acetate were measured to calculate the rate of exogenous glucose uptake and the regional oxidative metabolism (n = 15). Global and regional left ventricular function was evaluated by contrast ventriculography at baseline (n = 26) and after revascularization (n = 12). Transmural myocardial biopsies from the collateral-dependent area were obtained in seven patients during bypass surgery and analyzed by optical and electron microscopy. According to resting regional wall motion, patients were separated into groups with and without dysfunction of the collateral-dependent segments. In patients with normal wall motion (n = 9), regional myocardial blood flow, oxidative metabolism, and glucose uptake were similar among collateral-dependent and remote segments. By contrast, in patients with regional dysfunction (n = 17), collateral-dependent segments had lower myocardial blood flow (77 +/- 25 versus 95 +/- 27 mL.min-1.100 g-1, p < 0.001), smaller k values (slope of 11C clearance reflecting oxidative metabolism, 0.049 +/- 0.015 versus 0.068 +/- 0.020 min-1, p < 0.001) and higher glucose uptake (relative 18F-deoxyglucose-to-flow ratio of 1.9 +/- 1.6 versus 1.2 +/- 0.2, p < 0.05) compared with remote segments. However, myocardial blood flow and k values were similar among collateral-dependent segments of patients with and without segmental dysfunction. After intravenous dipyridamole, collateral-dependent myocardial blood flow increased from 78 +/- 5 to 238 +/- 54 mL.min-1.100 g-1 in three patients with normal wall motion and from 88 +/- 17 to only 112 +/- 44 mL.min-1.100 g-1 in eight patients with regional dysfunction. There was a significant (r = -0.85, p < 0.001) inverse correlation between wall motion abnormality and collateral flow reserve. Analysis of the tissue samples obtained at the time of bypass surgery showed profound structural changes in dysfunctioning collateral-dependent areas, including cellular swelling, loss of myofibrillar content, and accumulation of glycogen. Despite these alterations, the regional wall motion score improved significantly in the patients studied before and after revascularization (from 3.8 +/- 1.3 to 0.8 +/- 0.9, p < 0.005). In a subgroup of patients with noninfarcted collateral-dependent myocardium, immature or insufficiently developed collaterals do not provide adequate flow reserve. Despite nearly normal resting flow and oxygen consumption, these collateral-dependent segments exhibit chronically depressed wall motion and demonstrate marked ultrastructural alterations on morphological analysis. We propose that these alterations result from repeated episodes of ischemia as opposed to chronic hypoperfusion and represent the flow, metabolic, and morphological correlates of myocardial "hibernation."

Estradiol-produced modifications on the response to glucose of hepatocytes from fasted rats.

Estradiol treatment modified the metabolic responses of fasted rat hepatocytes to exogenous glucose with respect to glucose utilization and cytosolic NADPH-generating enzymes. The estrogen abolished the glucose-stimulated gluconeogenic capacity displayed by control rat cells while promoting a net uptake of exogenous glucose and enhancing the glucose-6-phosphate dehydrogenase activity. Estradiol also caused an increase in the activity of the isocitrate dehydrogenase that may be related to the enhanced needs of NADPH by hepatocytes for steroid hormone catabolism.

Increased uptake of 18F-fluorodeoxyglucose in postischemic myocardium of patients with exercise-induced angina.

Regional myocardial perfusion and exogenous glucose uptake were assessed with rubidium-82 (82Rb) and 18F-2-fluoro-2-deoxyglucose (FDG) in 10 normal volunteers and 12 patients with coronary artery disease and stable angina pectoris by means of positron emission tomography. In patients at rest, the myocardial uptake of 82Rb and FDG did not differ significantly from that measured in normal subjects. The exercise test performed within the positron camera in eight patients produced typical chest pain and ischemic electrocardiographic changes in all. In each of the eight patients a region of reduced cation uptake was demonstrated in the 82Rb scan recorded at peak exercise, after which uptake of 82Rb returned to the control value 5 to 14 min after the end of the exercise. In these patients, FDG was injected in the recovery phase when all the variables that were altered during exercise, including regional myocardial 82Rb uptake, had returned to control values. In all but one patient, FDG accumulation in the regions of reduced 82Rb uptake during exercise was significantly higher than that in the nonischemic regions, i.e., the ones with a normal increment of 82Rb uptake on exercise. In the nonischemic areas, FDG uptake was not significantly different from that found in normal subjects after exercise. In conclusion, myocardial glucose transport and phosphorylation seem to be enhanced in the postischemic myocardium of patients with exercise-induced ischemia.

Reversibility of cardiac wall-motion abnormalities predicted by positron tomography.

Positron emission tomography (PET) can be used with nitrogen-13-ammonia (13NH3) to estimate regional myocardial blood flow, and with fluorine-18-deoxyglucose (18FDG) to measure exogenous glucose uptake by the myocardium. We used PET to predict whether preoperative abnormalities in left ventricular wall motion in 17 patients who underwent coronary-artery bypass surgery were reversible. The abnormalities were quantified by radionuclide or contrast angiography or both, before and after grafting. PET images were obtained preoperatively. Abnormal wall motion in regions in which PET images showed preserved glucose uptake was predicted to be reversible, whereas abnormal motion in regions with depressed glucose uptake was predicted to be irreversible. According to these criteria, abnormal contraction in 35 of 41 segments was correctly predicted to be reversible (85 percent predictive accuracy), and abnormal contraction in 4 of 26 regions was correctly predicted to be irreversible (92 percent predictive accuracy). In contrast, electrocardiograms showing pathological Q waves in the region of asynergy predicted irreversibility in only 43 percent of regions. We conclude that PET imaging with 13NH3 to assess blood flow and 18FDG to assess the metabolic viability of the myocardium is an accurate method of predicting potential reversibility of wall-motion abnormalities after surgical revascularization.

Effect of insulin on glucose uptake in near-term fetal lambs.

Glucose clamp experiments were performed in 27 chronically catheterized, late-gestation fetal lambs in order to measure the effect of fetal insulin concentration on fetal glucose uptake at a constant glucose concentration. Fetal arterial blood glucose concentration was measured over a 30-min control period and then maintained at the control value by a variable glucose infusion into the fetus while insulin was infused at a constant rate into the fetus. Plasma insulin concentration increased from 21 +/- 10 (SD) to 294 +/- 179 (SD) microU X ml-1. The exogenous glucose infusion rate necessary to maintain constant glycemia during the plateau hyperinsulinemia averaged 4.3 +/- 1.6 (SD) mg X min-1 X kg-1. In a subset of 13 animals, total fetal exogenous glucose uptake (FGU; sum of glucose uptake from the placenta via the umbilical circulation plus the steady-state exogenous glucose infusion rate) was measured during the control and hyperinsulinemia period. FGU was directly related to insulin concentration (y = 4.24 + 0.07x) at insulin levels less than 100 microU/ml and increased 132% above control at insulin levels above 100 microU/ml. Hyperinsulinemia did not affect fetal glucose uptake from the placenta via the umbilical circulation. These studies demonstrate that insulin concentration is a major factor controlling glucose uptake in the near-term fetal lamb, and that an increase of fetal insulin does not affect the transport of glucose to the fetus from the placenta.

Granulocytes utilize different energy sources for movement and phagocytosis.

Granulocytes depend on anaerobic glycolysis for the energy required for chemotaxis, phagocytosis, and microbial killing. Two potential sources of the needed glucose are available: exogenous glucose and intracellular glycogen. These studies demonstrate that chemotaxin-induced movement of granulocytes induces accelerated uptake of exogenous glucose while phagocytosis does not, presumably utilizing instead the relatively slow process of glycogenolysis. As measured by incorporation of extracellular radiolabeled hexoses [1-14C]glucose or [3H]deoxyglucose), the soluble chemotaxin-aggregants of granulocytes, nF-met-leu-phe, C5ades arg, bacterial filtrate, or arachidonic acid all augment transmembrane hexose uptake. This insulin-like activity closely parallels the dose-related effects of these agents on induction of granulocyte aggregation and chemotaxis. Insulin, itself, affects glucose transport minimally and mainly at supraphysiologic concentrations. In contrast, phagocytic stimuli fail to enhance hexose uptake at all, despite stimulating catabolism of glucose, which in turn is probably generated by glucogenolysis. these data show that granulocytes, whose motile function occurs in glucose-rich milieu, alter in tandem their cellular glucose uptake with their movement response. For phagocytosis, which often occurs in hypoglycotic, purulent exudates, granulocytes depend on stored energy supplies--probably glycogen. This coordination may be crucial in supporting granulocyte antimicrobial activity during acute inflammation.

Carbohydrate metabolism in the rat epididymis: evidence that glucose is taken up by tissue slices and isolated cells by a process of facilitated transport.

An examination has been made of factors which influence the rate at which exogenous glucose is utilized by tissue slices and isolated cells prepared from the epididymis of rats with ligated efferent ducts. The uptake of exogenous glucose by tissue slices was unaffected by the addition of testosterone, dihydrotestosterone or carnitine but was reduced by theophylline and, in the caput epididymidis, was stimulated by insulin. Mannose was also utilized by epididymal tissue but fructose and galactose were utilized little, if at all. Galactose, arabinose and 1–0-methylglucose were ineffective in altering the rate at which exogenous glucose was taken up by isolated cells, whereas 3–0-methylglucose, 5-thio-D-glucose and 2-deoxy-D-glucose reduced the rate of glucose uptake, as did phloridzin and phloretin which inhibit membrane transport of hexoses in other tissues. The reduced rate of glucose uptake by epididymal cells in the presence of the nonmetabolizable sugar, 3–0-methylglucose, was shown to be due to competitive inhibition. By comparing the distribution space of glucose in isolated cells with that of substances which are normally excluded from entry into cells, it was evident that the extra- and intracellular concentrations of glucose were greatly displaced from equilibrium values. It is concluded that glucose enters epididymal cells with difficulty but that uptake occurs by a process of facilitated transport.

Inhibition of Insulin Release in Infants Undergoing Deep Hypothermic Cardiovascular Surgery

Abstract Plasma immunoreactive insulin and glucose levels were studied in infants undergoing deep hypothermic cardiovascular surgery. In six receiving glucose infusions, marked hyperglycemia developed when body temperature was lowered below 30°C. With cooling, plasma immunoreactive insulin levels fell or remained low despite the development of hyperglycemia. On rewarming, plasma insulin concentrations rose markedly, and glucose levels fell despite continued glucose administration. In three infants given saline infusions rather than glucose, plasma glucose and immunoreactive insulin levels remained relatively stable during cooling. Five of these patients were studied when unanesthetized and at normal temperatures. Similar glucose infusions produced much smaller increases in plasma glucose levels, and yet circulating immunoreactive insulin levels increased. These observations indicate that reduction of exogenous glucose uptake is associated with a marked reversible inhibition of insulin release in infants u...