scholarly journals Regulation of carbohydrate metabolism in lymphoid tissue. Quantitative aspects of [U-14C]glucose oxidation by rat spleen slices

1975 ◽  
Vol 148 (3) ◽  
pp. 583-594 ◽  
Author(s):  
D Suter ◽  
M J Weidemann
Keyword(s):  
Lymphoid Tissue ◽  
Glucose Utilization ◽  
Normal Values ◽  
Lactate Production ◽  
Pentose Phosphate ◽  
Glycolytic Metabolism ◽  
Anaerobic Conditions ◽  
Maximum Value ◽  
Nadh Ratio ◽  
Regulation Of Carbohydrate Metabolism

When washed spleen slices from fed rats are incubated with 3 mm-[U-14C]glucose, the rate of glucose utilization (46.2 mumol/h per g dry wt.) is sufficient to account, theoretically, for 80% of the O2 consumption. Measurement of net lactate production, however, and the fate of the radioactive carbon, indicates that the contribution of glucose to the respiratory fuel of the tissue is only 25-30% whereas 60-70% of the glucose utilized is converted into lactate. At saturating glucose concentrations (above 5 mm) its contribution to the respiratory fuel of the slice is increased to a maximum value of 34-39%. Only 2% of the glucose utilized is metabolized via the oxidative steps of the pentose phosphate pathway. Starvation for 72 h marginally increases both the rate of glucose utilization (by 21%) and its net contribution to the respiratory fuel (by 29%). Insulin, glucagon, adrenaline and adenosine 3′:5′-cyclic monophosphate have no significant effect on either the rate of glucose utilization or on the pattern of radioactive isotope distribution. The uptake of glucose is increased by only 20%, whereas the production of lactate doubles when slices are incubated under anaerobic conditions. In assessing the suitability of spleen slices for metabolic studies, the only serious major perturbation, compared with the freeze-clamped organ, is an elevated mitochondrial [NAD+]/[NADH] ratio (connected with increased endogenous NH3 production) that is partially restored to normal values on incubation with glucose. Equal proportions of erythrocytes and leucocytes are found in the washed spleen slice. Metabolic contributions of the constituent cell populations in the washed slice are calculated and it is concluded that lymphocytes account for the major part of the glycolytic metabolism (80-90%), whereas the contribution of erythrocytes is insignificant.

Control of glycogen utilization and glucose uptake in the anaerobic turtle heart

1963 ◽  
Vol 205 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Robert B. Reeves
Keyword(s):  
Glucose Uptake ◽  
Specific Activity ◽  
Lactate Production ◽  
Maximal Rate ◽  
Anaerobic Conditions ◽  
Exogenous Glucose ◽  
Maximum Value ◽  
Glycogen Utilization ◽  
Glycogen Stores ◽  
Turtle Heart

Glucose uptake and lactate production of isolated, perfused turtle ( Pseudemys scripta) hearts were measured under anaerobic conditions. At low pressure-volume workloads the hearts used glycogen stores rather than exogenous glucose to provide hexose substrate for glycolysis. Glycogenolysis increased in proportion to increased workload up to a critical maximum value for each heart. Increase of workload beyond this critical point was associated with utilization of exogenous glucose or, in the absence of glucose, with mechanical failure of the heart. Glucose-U-C14 was quantitatively (98%) converted into lactate, and neither dilution of exogenous glucose specific activity nor incorporation of label into glycogen or fatty acids occurred. The maximal rate of glycogenolysis was found to be a linear function of initial glycogen concentration. It is concluded that the input of hexose units into glycolysis is regulated jointly by hexokinase and phosphorylase; however, the known properties of these two enzymes will not fully account for all the features of this regulation.

scholarly journals Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3018
Author(s):  
Marek Samec ◽  
Alena Liskova ◽  
Lenka Koklesova ◽  
Kevin Zhai ◽  
Elizabeth Varghese ◽  
...  
Keyword(s):  
Cancer Metabolism ◽  
Glucose Transporter ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Lactate Production ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Effective Prevention ◽  
Anti Cancer ◽  
Glucose 6 Phosphate Dehydrogenase

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

Carbohydrate metabolism by primary cultures of rabbit proximal tubules

1989 ◽  
Vol 256 (3) ◽  
pp. C532-C539 ◽  
Author(s):  
M. J. Tang ◽  
K. R. Suresh ◽  
R. L. Tannen
Keyword(s):  
Pyruvate Kinase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Cultured Cells ◽  
Primary Cultures ◽  
Lactate Production ◽  
Proximal Tubules ◽  
Glycolytic Metabolism ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular

Renal proximal tubular epithelia were used to assess the factors responsible for the induction of glycolysis in cultured cells. Primary cultures of rabbit proximal tubules, which achieved confluency at 6 days, exhibited hormonal responsiveness and brush-border characteristics typical of proximal tubular cells. Beginning at day 4, these cultured cells exhibited increased glycolytic metabolism reflected by enhanced glucose uptake and lactate production, along with parallel increases in activity of the glycolytic enzymes, pyruvate kinase and lactate dehydrogenase. The gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase (FDP), were downregulated, and the cultured cells exhibited lower oxygen consumption rates than fresh tubules. Cells grown on a rocker, to mitigate hypoxia, exhibited a metabolic and enzymatic profile similar to cells grown under still conditions. ATP levels in cultured cells were higher than in fresh tubules. Furthermore, pyruvate kinase activity was higher in cells grown in media containing 0.5 as contrasted with 25 mM glucose. The enhanced glycolytic metabolism exhibited by cultured proximal tubular cells appears to be a characteristic of proliferation and is not a response to hypoxia, the Pasteur effect, or environmental glucose.

METABOLISM OF RAM TESTICULAR SPERMATOZOA IN THE PRESENCE OF TESTOSTERONE AND RELATED STEROIDS

1970 ◽  
Vol 65 (3) ◽  
pp. 565-576 ◽  
Author(s):  
J. K. Voglmayr ◽  
R. N. Murdoch ◽  
I. G. White
Keyword(s):  
Aerobic Glycolysis ◽  
Rete Testis ◽  
Glycolytic Metabolism ◽  
Anaerobic Conditions ◽  
Aerobic Conditions ◽  
Testicular Spermatozoa ◽  
Almost All ◽  
Oxidation Of Glucose

ABSTRACT The effects of testosterone* and related steroids on the oxidative and glycolytic metabolism of freshly collected ram testicular spermatozoa and of spermatozoa stored under air in rete testis fluid for 3 days at 3°C have been studied. When freshly collected testicular spermatozoa were incubated with glucose under aerobic conditions only a small proportion of the utilized glucose could be accounted for as lactate. The addition of a number of steroids, including testosterone, androstanedione, 5β-androstanedione, androsterone, epiandrosterone and 5β-androsterone, greatly increased aerobic glycolysis, the oxidation of the substrate and the proportion of the utilized substrate converted to lactic acid. After 3 days storage at 3°C, testicular spermatozoa respired at a greater rate than spermatozoa freshly collected from the testes. Although the stimulating effect of steroids on aerobic glycolysis increased after storage, they depressed rather than stimulated the oxidation of glucose by stored testicular spermatozoa. With the exception of androstanedione, which slightly stimulated glycolysis, storage of testicular spermatozoa for 3 days in the presence of steroids did not significantly influence their subsequent metabolism when washed free of the steroids. Both freshly collected and stored ram testicular spermatozoa displayed a marked Pasteur effect, and utilized more glucose and produced more lactate under anaerobic than under aerobic conditions. In the absence of oxygen the steroids did not stimulate glycolysis to any extent. However, epiandrosterone depressed the glycolysis of freshly collected spermatozoa under anaerobic conditions and after storage, 5β-androsterone had a similar effect. Androstanedione, 5β-androstanedione, epiandrosterone and 5β-androsterone were the most effective steroids in altering the metabolism of testicular spermatozoa and, under almost all conditions of incubation, depressed the synthesis of amino acids from glucose. The results suggest that the effects of testosterone and related steroids in vitro may depend on the age of the spermatozoa after their release from the Sertoli cells; the steroid effects may have important consequences in vivo in relation to sperm maturation.

Effect of perfusate glucose concentration on rat lung glycolysis.

1979 ◽  
Vol 236 (3) ◽  
pp. E229 ◽  
Author(s):  
J S Kerr ◽  
N J Baker ◽  
D J Bassett ◽  
A B Fisher
Keyword(s):  
Glucose Concentration ◽  
Glucose Utilization ◽  
Glycogen Content ◽  
Lactate Production ◽  
Bicarbonate Buffer ◽  
Exogenous Glucose ◽  
Low Glucose ◽  
The Difference ◽  
Endogenous Substrates ◽  
The Relationship

We investigated the relationship between perfusate concentration of glucose and its utilization and lactate production derived from exogenous glucose and from metabolism of endogenous substrates. Isolated rat lungs were ventilated with 5% CO2 in air and perfused for 100 min with Krebs-Ringer bicarbonate buffer containing 3% bovine serum albumin, 10(-2) U/ml insulin, [U-14C]glucose and [5-3H]glucose. Glucose utilization, total lactate production, [14C]lactate production, and 3H2O production were measured. The apparent Km and Vmax for glucose utilization were 3.4 mM and 72.5 mumol/g dry wt per h, respectively. Lactate production from endogenous substrates, calculated as the difference between total and [14C]lactate, was 37.6 +/- 2.2 mumol/g dry wt (n = 36); it was unaffected by perfusate glucose concentration and by omission of insulin, but increased threefold with anoxia. Lactate production from 1.5 mM glucose was significantly less (P less than 0.02) with insulin omitted. Glycogen content was unchanged during perfusion without glucose. These results suggest that: 1) protein catabolism contributes to lung lactate production; 2) glucose utilization by lung is not maximal at resting physiological glucose concentrations; and 3) insulin is required at low glucose concentrations for maximal glycolytic rates.

Effects of substrate and hypoxia on smooth muscle metabolism and contraction

1989 ◽  
Vol 256 (4) ◽  
pp. C719-C727 ◽  
Author(s):  
I. R. Wendt
Keyword(s):  
Smooth Muscle ◽  
Oxygen Consumption ◽  
Urinary Bladder ◽  
Heat Production ◽  
Lactate Production ◽  
Muscle Metabolism ◽  
Anaerobic Conditions ◽  
Aerobic Conditions ◽  
Sufficient Energy ◽  
Rabbit Urinary Bladder

Suprabasal heat production, oxygen consumption, and lactate production were measured, together with force, in 30-s isometric contractions of longitudinal smooth muscle from rabbit urinary bladder at 27 degrees C. Either glucose or pyruvate was provided as exogenous substrate. Under aerobic conditions with glucose as substrate, force averaged 95 mN/mm2 and heat production 121 mJ/g. Oxygen consumption (0.18 mumol/g) could account for only two-thirds of the total energy expenditure represented as heat production. The remaining one-third was accounted for by aerobic lactate production (0.36 mumol/g). When pyruvate replaced glucose as substrate, both the force developed and the total heat liberated were unchanged. Oxygen consumption, however, increased by approximately 40% (to 0.25 mumol/g) and was able to fully account for the measured heat production. The frequency of spontaneous contractions under aerobic conditions was always reduced in the presence of pyruvate. Under anaerobic conditions force was essentially unaltered, and heat production was only slightly reduced (101 mJ/g) with glucose present. Lactate production increased threefold over that under aerobic conditions. With pyruvate as substrate both force and heat production declined markedly (to less than 5% of the aerobic values). The results indicate that under aerobic conditions and with glucose as substrate, smooth muscle of rabbit urinary bladder generates about one-third of its suprabasal energy requirements through glycolysis and that glycolysis can be further accelerated under anaerobic conditions to provide sufficient energy to sustain contraction. If pyruvate replaces glucose as substrate, the metabolism shifts to being virtually all oxidative, and contraction can no longer be sustained in the absence of oxygen.

scholarly journals Lactate production is the major metabolic fate of glucose in splenocytes and is altered in spontaneously diabetic BB rats

1990 ◽  
Vol 272 (2) ◽  
pp. 445-452 ◽  
Author(s):  
C J Field ◽  
G Wu ◽  
M D Métroz-Dayer ◽  
M Montambault ◽  
E B Marliss
Keyword(s):  
Glucose Utilization ◽  
Lactate Production ◽  
Resting Cells ◽  
Metabolic Fate ◽  
Con A ◽  
Normal Cells ◽  
Immunological Activation ◽  
Proliferation Of Lymphocytes ◽  
Lactate And Pyruvate

Enhanced glucose metabolism is necessary to support the activation and proliferation of lymphocytes. To define further quantitatively the metabolic fates of glucose and assess glucose utilization both in normal cells and in an autoimmune disease with abnormal lymphocytes, [U-14C]glucose conversion into 14CO2 and the production of lactate and pyruvate were measured in splenocytes. Cells from non-diabetes-prone (BBn) and spontaneously diabetic (BBd) rats were studied both freshly isolated ‘resting’ and cultured for 96 h with and without concanavalin A (Con A) stimulation. (1) Lactate was confirmed to be the major end product in both freshly isolated (53% of utilized glucose) and unstimulated cultured (62% of utilized glucose) cells from BBn animals studied at (2-8) x 10(6) cells/ml concentration. The use of concentrations from 10 x 10(6) to 300 x 10(6) cells/ml resulted in progressively less lactate production per 10(6) splenocytes. (2) Cells from BBd animals after stimulation with Con A incorporated less [3H]thymidine and produced significantly less lactate (155 +/- 14 versus 305 +/- 24 nmol/2 h per 10(6) cells) than did BBn cells (P less than 0.05). (3) However, more lactate (101 +/- 8 versus 78 +/- 6 nmol/5 h per 10(6) cells) was produced by ‘resting’ cells from BBd animals compared with BBn (P less than 0.03), and this difference was sustained after 4 days in culture. (4) Significantly greater amounts of pyruvate were produced by BBd than by BBn cells, particularly when stimulated with Con A, suggesting an alteration in the availability of reducing equivalents in BBd cells. (5) These results are consistent with prior metabolic as well as immunological ‘activation’ of cells in vivo in the BB diabetic animals.

scholarly journals Glucose metabolism and its regulation in pieces of perirenal adipose tissue from foetal lambs

1983 ◽  
Vol 210 (3) ◽  
pp. 677-683 ◽  
Author(s):  
J P Robertson ◽  
A Faulkner ◽  
R G Vernon
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Pyruvate Dehydrogenase ◽  
Glucose Utilization ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Acid Cycle ◽  
Near Term ◽  
Glucose 6 Phosphate Dehydrogenase

1. The following were measured in pieces of perirenal adipose tissue obtained from foetal lambs at about 120 days of gestation or within 3 days of term, and 9-month-old sheep: the rates of synthesis from glucose of fatty acids, acylglycerol glycerol, pyruvate and lactate; the rate of glucose oxidation to CO2 and the proportions contributed by the pentose phosphate cycle, pyruvate dehydrogenase and the tricarboxylic acid cycle; the activities of hexokinase, glucose 6-phosphate dehydrogenase, phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase. 2. The total rate of glucose utilization was lower in pieces of adipose tissue from near-term lambs than 120-day foetal lambs and the pattern of glucose metabolism differed, with, for example, a much smaller proportion of glucose carbon being used for fatty acid synthesis, whereas a greater proportion of glucose oxidation occurred via the tricarboxylic acid cycle in the near-term lambs. In general, these differences in glucose metabolism were not associated with differences in the activities of the various enzymes listed above. 3. The rates of glucose utilization per fat-cell by 120-day foetal lambs and 9-month-old sheep were very similar but, again, the proportions metabolized to the various products differed. In particular, there was a smaller proportion of glucose oxidized via the pentose phosphate cycle and a greater proportion oxidized via pyruvate dehydrogenase and the tricarboxylic acid cycle in adipose tissue from foetal lambs. These differences were matched by a lower activity of glucose 6-phosphate dehydrogenase and a higher pyruvate dehydrogenase activity in fat-cells from the foetal lambs.

scholarly journals TNF-α-Induced NF-κB Activation Stimulates Skeletal Muscle Glycolytic Metabolism Through Activation of HIF-1α

Endocrinology ◽  
2015 ◽  
Vol 156 (5) ◽  
pp. 1770-1781 ◽  
Author(s):  
A. H. V. Remels ◽  
H. R. Gosker ◽  
K. J. P. Verhees ◽  
R. C. J. Langen ◽  
A. M. W. J. Schols
Keyword(s):  
Oxidative Metabolism ◽  
Lactate Production ◽  
Quadriceps Muscle ◽  
Metabolic Adaptation ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Glycolytic Metabolism ◽  
Consistent Finding ◽  
Tnf Α ◽  
Muscle Biopsies

A shift in quadriceps muscle metabolic profile toward decreased oxidative metabolism and increased glycolysis is a consistent finding in chronic obstructive pulmonary disease (COPD). Chronic inflammation has been proposed as a trigger of this pathological metabolic adaptation. Indeed, the proinflammatory cytokine TNF-α impairs muscle oxidative metabolism through activation of the nuclear factor-κB (NF-κB) pathway. Putative effects on muscle glycolysis, however, are unclear. We hypothesized that TNF-α-induced NF-κB signaling stimulates muscle glycolytic metabolism through activation of the glycolytic regulator hypoxia-inducible factor-1α (HIF-1α). Wild-type C2C12 and C2C12-IκBα-SR (blocked NF-κB signaling) myotubes were stimulated with TNF-α, and its effects on glycolytic metabolism and involvement of the HIF pathway herein were investigated. As proof of principle, expression of HIF signaling constituents was investigated in quadriceps muscle biopsies of a previously well-characterized cohort of clinically stable patients with severe COPD and healthy matched controls. TNF-α increased myotube glucose uptake and lactate production and enhanced the activity and expression levels of multiple effectors of muscle glycolytic metabolism in a NF-κB-dependent manner. In addition, TNF-α activated HIF signaling, which required classical NF-κB activation. Moreover, the knockdown of HIF-1α largely attenuated TNF-α-induced increases in glycolytic metabolism. Accordingly, the mRNA levels of HIF-1α and the HIF-1α target gene, vascular endothelial growth factor (VEGF), were increased in muscle biopsies of COPD patients compared with controls, which was most pronounced in the patients with high levels of muscle TNF-α. In conclusion, these data show that TNF-α-induced classical NF-κB activation enhances muscle glycolytic metabolism in a HIF-1α-dependent manner.

Glycogen Synthetic Abilities of Actinomyces viscosus and Actinomyces naeslundii Freshly Isolated from Dental Plaque over Root Surface Caries Lesions and Non-carious Sites

1986 ◽  
Vol 65 (6) ◽  
pp. 899-902 ◽  
Author(s):  
K. Komiyamai ◽  
R.L. Khandelwal ◽  
D.E. Duncan
Keyword(s):  
Dental Plaque ◽  
Glucose Utilization ◽  
Root Surface ◽  
Resting Cells ◽  
Anaerobic Conditions ◽  
Total Acid ◽  
Actinomyces Naeslundii ◽  
Constant Ph ◽  
Caries Lesions ◽  
Root Surface Caries

Relative glycogen synthetic abilities of resting cells of fresh clinical isolates of Actinomyces viscosus and Actinomyces naeslundii originating from dental plaque samples over root surface caries lesions and non-carious sites were studied under anaerobic conditions at a constant pH of 7.0, with U-(14C)-glucose used as the carbon source. Although the rates of glucose utilization and total acid formation were essentially the same, A. viscosus strains isolated from root surface caries lesions showed glycogen synthetic abilities approximately two to seven times higher than did A. viscosus strains originating from non-carious sites, and also two to four times higher than did A. naeslundii strains originating from both carious and non-carious sites.

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