Role of glucose in corneal metabolism

1985 ◽  
Vol 249 (5) ◽  
pp. C409-C416 ◽  
Author(s):  
R. S. Thies ◽  
L. J. Mandel

Glucose catabolism by glycolysis and the Krebs cycle was examined in the isolated rabbit cornea incubated with [6-14C]glucose. The production of [14C]lactate and 14CO2 from this substrate provided minimal values for the fluxes through these pathways since the tissue was in metabolic steady state but not isotopic steady state during the 40-min incubation. The specific activity of lactate under these conditions was one-third of that for [6-14C]glucose, and label dilution by exchange with unlabeled alanine was minimal, suggesting that glycogen degradation was primarily responsible for this dilution of label in the Embden-Meyerhof pathway. In addition, considerable label accumulation was found in glutamate and aspartate. Calculations revealed that these endogenous amino acid pools were not isotopically equilibrated after the incubation period, suggesting that they were responsible for the isotopic nonsteady state by exchange dilution through transaminase reactions with labeled intermediates. An estimate of glucose oxidation by the Krebs cycle, which was corrected for label dilution by exchange, indicated that glucose could account for most of the measured corneal oxygen consumption that was coupled to oxidative phosphorylation. A minor component of this respiration could not be accounted for by glucose or glycogen oxidation. Additional experiments suggested that endogenous fatty acid oxidation was probably also active under these conditions. Finally, reciprocal changes in plasma membrane Na+-K+-ATPase activity induced by ouabain and nystatin were found to concomitantly alter oxygen consumption rates and [14C]lactate production from [6-14C]glucose. These results demonstrated the capacity for regulating glycolysis and the Krebs cycle in response to changing energy demands in the cornea.

1989 ◽  
Vol 257 (5) ◽  
pp. E782-E789 ◽  
Author(s):  
C. M. Donovan ◽  
M. J. Pagliassotti

Constant infusions of cold molar lactate (178.0 +/- 1.6 mumol.kg-1.min-1), [U-14C]lactate (0.50 muCi/min), and [6-3H]glucose (0.5 muCi/min) were employed to study the effects of endurance training (running 1 h/day, at 38 m/min, 10% grade) on lactate clearance in resting, hyperlactatemic rats. Before infusion, resting blood lactate levels were not significantly different between controls, 1.10 +/- 0.04 mM, and trained animals, 1.16 +/- 0.04 mM. Lactate levels increased significantly during the infusion period, attaining steady-state mixed venous concentrations of 11.32 +/- 0.24 mM and 5.44 +/- 0.09 mM, respectively, for controls and trained animals. Lactate clearance rates, based on net lactate removal (i.e., not tracer-estimated lactate removal), were twofold greater in trained animals vs. controls, 33.0 +/- 0.7 and 15.4 +/- 0.4 ml.kg-1. min-1, respectively. Lactate specific activity values during the infusion period were not significantly different between controls, 22,243 +/- 236 dpm/mumol, and trained animals, 21,270 +/- 374 dpm/mumol, indicating similar endogenous dilution of the pyruvate-lactate pool. For both control and trained animals, essentially 100% of the 14C infused as lactate was recovered as either glucose or CO2; however, trained animals demonstrated a 25% greater rate of gluconeogenesis. At a given lactate production rate, trained animals maintain lower lactate levels through enhanced clearance via gluconeogenesis and oxidation.


1982 ◽  
Vol 243 (1) ◽  
pp. H128-H132 ◽  
Author(s):  
R. Odessey ◽  
K. V. Chace

The utilization of endogenous stores by rabbit aorta in vitro was measured. In substrate-free medium glycogen disappearance may account for less than 20% of the tissue O2 consumption during incubations of less than 2-3 h. At longer times (or in the presence of glucose) glycogen catabolism is negligible. Calculations from the rate of proteolysis suggest that oxidation of endogenously generated amino acids accounts for less than 7-10% of the oxygen consumption. Furthermore, the presence of amino-oxyacetate, a transaminase inhibitor, did not alter the ATP-ADP ratio. By contrast, measurements of the disappearance of tissue triglyceride indicate that endogenous lipid could meet the fuel requirements of the aorta. Direct measurement of intracellular fatty acid oxidation was obtained by measuring acyl carnitine specific activity and 14CO2 production from [1-14C]palmitate. Fatty acid oxidation could account for at least 90% of the total O2 consumption, and 83% of the fatty acids consumed were derived from endogenous tissue stores. Octanoate was found to inhibit both exogenous and endogenous fatty acid oxidation. These findings may indicate that shorter-chain fatty acids may be preferentially utilized by the aorta.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Kedryn K Baskin ◽  
Chad E Grueter ◽  
Christine M Kusminski ◽  
Philipp E Scherer ◽  
Rhonda Bassel-Duby ◽  
...  

Background: The heart is a metabolic organ that primarily utilizes fatty acids as energy substrate. While it is well established that the heart is metabolically flexible, the transcriptional network regulating cardiac metabolism is only partially understood. We have previously demonstrated that cardiac overexpression of Med13, a component of the Mediator Complex that regulates transcription, results in a lean phenotype with enhanced basal metabolic rates. We now investigate the mechanisms contributing to metabolic changes in mice with cardiac over-expression of Med13(Med13cTg). Methods and Results: Cardiac fludeoxyglucose (18F-FDG)-PET imaging analysis revealed that Med13cTg hearts take up more glucose than wild type littermates. To determine pathways responsible for enhanced glucose uptake, ventricles from Med13cTg mice were subjected to RNA-seq and metabolomic analysis. The expression of fatty acid oxidation genes was decreased in Med13cTg hearts, accompanied by an increase in acyl CoA and a decrease in acetyl CoA. These data suggest that beta oxidation is decreased in Med13cTg hearts. Mitochondria function was therefore determined in Med13cTg hearts by performing electron-flow analyses and assessing oxygen consumption rates. Indeed, oxygen consumption rates were decreased in mitochondria isolated from Med13cTg hearts. Expression of Krebs Cycle genes and corresponding intermediary metabolites were also decreased in Med13cTg hearts, suggesting decreased flux through this pathway as well. Conclusions: Overexpression of Med13 in the heart increases glucose uptake and decreases fatty acid oxidation in the heart. We speculate that Med13 transcriptionally regulates key mediators of cardiac metabolism. The mechanisms by which this occurs are currently under investigation.


1973 ◽  
Vol 58 (2) ◽  
pp. 332-339 ◽  
Author(s):  
Miriam D. Rosenthal ◽  
Joseph B. Warshaw

Chick embryo heart cells in tissue culture actively oxidize [1-14C]palmitate to 14CO2. Fatty acid oxidation by cell monolayers was linear with time and increasing protein concentration. The addition of carnitine to the assay medium resulted in a 30–70% increase in the rate of fatty acid oxidation. The specific activity of palmitic acid oxidation did not change significantly with time in culture and was also the same in rapidly proliferating and density-inhibited cell cultures. Addition of unlabeled glucose to the assay medium resulted in a 50% decrease in 14CO2 production from [1-14C]palmitate. Conversely, palmitate had a similar sparing effect on [14C]glucose oxidation to 14CO2. Lactate production accounted for most of the glucose depleted from the medium and was not inhibited by the presence of palmitate in the assay. Thus, the sparing action of the fatty acids on glucose oxidation appears to be at the mitochondrial level. The results indicate that although chick heart cells in culture are primarily anaerobic, they can oxidize fatty acid actively.


1987 ◽  
Vol 252 (4) ◽  
pp. E519-E524 ◽  
Author(s):  
J. R. Milley

The goal of this study was to test the hypothesis that the rate of fetal protein synthesis decreases during fetal hypoxia. Catheters were inserted into 13 sheep fetuses under maternal spinal and local fetal anesthesia. Five days after surgery, an infusion of L-[1-14C]tyrosine (0.05-0.25 muCi/min) was begun. Measurements were first made when tyrosine-specific activity reached steady state at 3 h and then again 3 h after fetal oxygen delivery was reduced by lowering the maternal inspired oxygen concentration. Fetal tyrosine uptake across the umbilical circulation was 1.34 +/- 0.20 mumol X kg-1 X min-1 during normoxia and decreased to 0.72 +/- 0.12 mumol X kg-1 X min-1 during hypoxia (P = 0.017). Tyrosine use from the plasma compartment was 1.25 +/- 0.18 mumol X kg-1 X min-1 during normoxia and decreased to 0.64 +/- 0.12 mumol X kg-1 X min-1 (P = 0.0005) during hypoxia. Fetal tyrosine use decreased during reduced oxygen delivery because the rate of tyrosine use for fetal protein synthesis decreased from 0.97 +/- 0.17 to 0.38 +/- 0.09 mumol X kg-1 X min-1 (P = 0.0004). Fetal oxygen consumption decreased by 40 mumol X kg-1 X min-1 during hypoxia. Decreased protein synthesis reduced the energy needed for protein synthesis and explained 28 mumol X kg-1 X min-1 of this reduction.


1988 ◽  
Vol 252 (2) ◽  
pp. 617-620 ◽  
Author(s):  
T Beccari ◽  
A Orlacchio ◽  
J L Stirling

beta-N-Acetylhexosaminidase from mouse tissue was separated into its constituent isoenzymes on DEAE-cellulose and its activity was monitored with 4-methylumbelliferyl-beta-N-acetylglucosamine and 4-methylumbelliferyl-beta-N-acetylglucosamine 6-sulphate. Forms corresponding to the human isoenzymes A (acidic), B (basic) and an ‘intermediate’ form were present in mouse liver and spleen, whereas in kidney the B and ‘intermediate’ forms predominated, with A present only as a minor component. In brain the ‘intermediate’, A and C activities were detected. Testis had predominantly A activity, whereas epididymis, the tissue with the highest specific activity of beta-N-acetylhexosaminidase, had an abundance of the ‘intermediate’ form, but was almost entirely lacking in the A form.


1985 ◽  
Vol 249 (6) ◽  
pp. E595-E602 ◽  
Author(s):  
W. C. Stanley ◽  
E. W. Gertz ◽  
J. A. Wisneski ◽  
D. L. Morris ◽  
R. A. Neese ◽  
...  

To investigate the relationships between oxygen consumption (VO2) and the rates of systemic lactate appearance (Ra) and disappearance (Rd), six healthy males were studied at rest and during continuous graded exercise using a primed continuous infusion of lactate tracer. Subjects exercised for 6 min at 300, 600, 900, and 1,200 kg . m . min-1. L-(+)-[1-14C]lactate was infused intravenously, and arterial samples were drawn at rest and every 2 min throughout the exercise period. Ra and Rd were calculated using nonsteady-state equations. At rest Ra and Rd were 14.4 +/- 1.8 and 15.1 +/- 2.2 mumol . kg-1 . min-1, respectively. Near steady-state values were observed toward the end of the first two work loads. Ra and Rd values were 32.8 +/- 2.3 and 37.4 +/- 1.3 mumol . kg-1 . min-1 during min 5 and 6 at 300 kg . m . min-1 and were 59.1 +/- 2.6 and 55.4 +/- 2.3 mumol . kg-1 . min-1 during min 5 and 6 at 600 kg . m . min-1. Ra was significantly greater than Rd at both 900 and 1,200 kg . m . min-1. Ra and Rd averaged 145.4 +/- 10.5 and 110.2 +/- 5.6 mumol . kg-1 . min-1, respectively, during the last 2 min at 900 kg . m . min-1, and 309.4 +/- 20.8 and 169.7 +/- 10.6 mumol . kg-1 . min-1, respectively, at 1,200 kg . m . min-1.(ABSTRACT TRUNCATED AT 250 WORDS)


1993 ◽  
Vol 264 (4) ◽  
pp. E548-E560 ◽  
Author(s):  
P. C. Butler ◽  
A. Caumo ◽  
A. Zerman ◽  
P. C. O'Brien ◽  
C. Cobelli ◽  
...  

Measurement of glucose turnover under non-steady-state conditions has proven problematic. When the mass of the glucose pool is not changing (i.e., glucose concentrations are constant) non-steady-state error can be minimized if all glucose entering the circulation has the same specific activity as plasma [radioactive infused glucose (hot-GINF) method]. Alternatively, a second tracer can be used to measure the effective volume of glucose [variable-pV method of Issekutz (T. Issekutz, R. Issekutz, and D. Elahi. (Can. J. Physiol. 52:215-224, 1974)]. To determine whether these techniques provide concordant assessments of insulin action under non-steady-state conditions, glucose turnover was measured in six subjects. After initiation of insulin (0.6 mU.kg-1 x min-1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by approximately 100-120 min. In contrast, the traditional fixed-pV method of Steele (R. Steele, J. Wall, R. DeBodo, and N. Altszuler. Am. J. Physiol. 187:15-24 1956) underestimated turnover (P < 0.01) resulting in apparent complete suppression of glucose release within approximately 40 min (P < 0.01 vs. other methods). The hot-GINF and variable-pV methods also yielded similar estimates of turnover after discontinuation of insulin. Both indicated that resumption of hepatic glucose release was slower (P < 0.01) and fall of glucose uptake faster (P < 0.01) than suggested by the fixed-pV method. Thus both the hot-GINF and variable-pV methods avoid non-steady-state error introduced by the fixed-pV method and provide concordant assessments of the rate of onset and offset of insulin action.


1960 ◽  
Vol XXXV (IV) ◽  
pp. 575-584 ◽  
Author(s):  
C. Borel ◽  
J. Frei ◽  
A. Vannotti

ABSTRACT Enzymatic studies, on leucocytes of pregnant women, show an increase of the alkaline phosphatase activity and a decrease of the glucose consumption and lactate production, as well as of proteolysis. The oxygen consumption, with succinate as substrate, does not vary.


1979 ◽  
Vol 44 (3) ◽  
pp. 841-853 ◽  
Author(s):  
Zbyněk Ryšlavý ◽  
Petr Boček ◽  
Miroslav Deml ◽  
Jaroslav Janák

The problem of the longitudinal temperature distribution was solved and the bearing of the temperature profiles on the qualitative characteristics of the zones and on the interpretation of the record of the separation obtained from a universal detector was considered. Two approximative physical models were applied to the solution: in the first model, the temperature dependences of the mobilities are taken into account, the continuous character of the electric field intensity at the boundary being neglected; in the other model, the continuous character of the electric field intensity is allowed for. From a comparison of the two models it follows that in practice, the variations of the mobilities with the temperature are the principal factor affecting the shape of the temperature profiles, the assumption of a discontinuous jump of the electric field intensity at the boundary being a good approximation to the reality. It was deduced theoretically and verified experimentally that the longitudinal profiles can appreciably affect the longitudinal variation of the effective mobilities in the zone, with an infavourable influence upon the qualitative interpretation of the record. Pronounced effects can appear during the analyses of the minor components, where in the corresponding short zone a temperature distribution occurs due to the influence of the temperatures of the neighbouring zones such that the temperature in the zone of interest in fact does not attain a constant value in axial direction. The minor component does not possess the steady-state mobility throughout the zone, which makes the identification of the zone rather difficult.


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