Kinetics of glucose transport and sequestration in lactating bovine mammary glands measured in vivo with a paired indicator/nutrient dilution technique

2005 ◽  
Vol 99 (3) ◽  
pp. 799-806 ◽  
Author(s):  
Fulong Qiao ◽  
Donald R. Trout ◽  
Changting Xiao ◽  
John P. Cant

To quantify kinetics of mammary glucose utilization in vivo, 24 paired glucose and extracellular indicator ( p-aminohippuric acid) dilution curves across intact bovine mammary glands were obtained after bolus injections into the external iliac artery. Dilution curves were analyzed using a compartmental capillary, convolution integration model. Four candidate submodels of glucose transport and metabolism in capillary supply zones were fit to the glucose dilution curves and evaluated. Model I, with one extracellular compartment for glucose and first-order unidirectional uptake, failed, indicating that efflux of glucose from the intracellular space could not be ignored. Model II, with first-order exchanges between extracellular and intracellular compartments and sequestration from the latter, was overdefined because unidirectional clearance of glucose was at least five times the blood flow rate and 20 times the net clearance rate. Model III, combining extracellular and intracellular space into one compartment, was superior in its goodness-of-fit to curves and identifiability of parameters. Michaelis-Menten parameters of sequestration were not identifiable. Parameters of the optimal compartmental capillary, convolution integration model were applicable to both the dynamics of injected glucose dilution and the steady-state background arteriovenous difference of glucose. Glucose sequestration followed first-order kinetics between 0 and 7 mM extracellular glucose with an average rate constant of 0.006 s−1 or a clearance of 44 ml/s. The ratio of intracellular to extracellular glucose distribution space was 0.34, which is considerably lower than the expected intracellular volume and suggests an intracellular occlusion compartment with which extracellular glucose rapidly exchanges.

2005 ◽  
Vol 99 (3) ◽  
pp. 788-798 ◽  
Author(s):  
Fulong Qiao ◽  
Donald R. Trout ◽  
V. Margaret Quinton ◽  
John P. Cant

Thirty-three paired indicator/nutrient dilution curves across the mammary glands of four cows were obtained after rapid injection of para-aminohippuric acid (PAH) plus glucose into the external iliac artery. For the measurement of extracellular volume and kinetics of nutrient uptake from indicator dilution curves, several models of solute dispersion and disappearance have been proposed. The Crone-Renkin models of exchange in a single capillary assume negligible washout of solutes from the extracellular space and do not describe entire dilution curves. The Goresky models include a distribution of capillary transit times to generate whole system outflow profiles but require two indicators to parametize extracellular behavior. A compartmental capillary, convolution integration model is proposed that uses one indicator to account for the extracellular behavior of the nutrient after a paired indicator/nutrient injection. With the use of an iterative approach to least squares, unique solutions for nonexchanging vessel transit time μ and its variance σ were obtained from all 33 PAH curves. The average of heterogeneous vascular transit times was approximated as 2σ = 8.5 s. The remainder of indicator dispersion was considered to be due to washout from a well-mixed compartment representing extracellular space that had an estimated volume of 5.5 liters or 24% of mammary gland weight. More than 99% of the variation in the time course of venous PAH concentration after rapid injection into the arterial supply of the mammary glands was explained in an unbiased manner by partitioning the organ into a heterogeneous nonexchanging vessel subsystem and a well-mixed compartmental capillary subsystem.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Anna Gumieniczek ◽  
Anna Berecka-Rycerz ◽  
Rafał Pietraś ◽  
Izabela Kozak ◽  
Karolina Lejwoda ◽  
...  

A comparative study of chemical stability of terfenadine (TER) and itsin vivometabolite fexofenadine (FEX) was performed. Both TER and FEX were subjected to high temperature at different pH and UV/VIS light at different pH and then quantitatively analyzed using new validated LC-UV methods. These methods were used to monitor the degradation processes and to determine the kinetics of degradation for both the compounds. As far as the effects of temperature and pH were concerned, FEX occurred more sensitive to degradation than TER. As far as the effects of UV/VIS light and pH were concerned, the both drugs were similarly sensitive to high doses of light. Using all stress conditions, the processes of degradation of TER and FEX followed the first-order kinetics. The results obtained for these two antihistaminic drugs could be helpful in developing their new derivatives with higher activity and stability at the same time.


1939 ◽  
Vol 23 (1) ◽  
pp. 21-39 ◽  
Author(s):  
Aurin M. Chase ◽  
Emil L. Smith

1. Measurements of visual purple regeneration in solution have been made by a procedure which minimized distortion of the results by other color changes so that density changes caused by the regenerating substance alone are obtained. 2. Bleaching a visual purple solution with blue and violet light causes a greater subsequent regeneration than does an equivalent bleaching with light which lacks blue and violet. This is due to a photosensitive substance which has a gradually increasing effective absorption toward the shorter wavelengths. It is uncertain whether this substance is a product of visual purple bleaching or is present in the solution before illumination. 3. The regeneration of visual purple measured at 560 mµ is maximal at about pH 6.7 and decreases markedly at more acid and more alkaline pH's. 4. The absorption spectrum of the regenerating material shows only a concentration change during the course of regeneration, but has a higher absorption at the shorter wavelengths than has visual purple before illumination. 5. Visual purple extractions made at various temperatures show no significant difference in per cent of regeneration. 6. The kinetics of regeneration is usually that of a first order process. Successive regenerations in the same solution have the same velocity constant but form smaller total amounts of regenerated substance. 7. In vivo, the frog retina shows no additional oxygen consumption while visual purple is regenerating.


1995 ◽  
Vol 268 (4) ◽  
pp. E712-E721 ◽  
Author(s):  
J. H. Youn ◽  
J. K. Kim ◽  
G. M. Steil

The effects of insulin on extracellular glucose distribution and cellular glucose transport activity were studied by simultaneously analyzing the plasma kinetics of L-[1-14C]glucose and 3-O-[3H]methylglucose after an intravenous injection during saline or insulin infusion (euglycemic glucose clamp) in conscious rats (n = 7 for each). The time profiles of plasma L-glucose were almost superimposable in the two protocols, and compartmental analysis showed that neither distribution volumes nor distribution rate constants were affected with insulin (P > 0.05 for all), suggesting that glucose distribution within the extracellular space was not influenced with insulin. In contrast, the time profile of plasma 3-O-methylglucose (3-MG) was markedly altered with insulin; the initial decrease was much faster during insulin infusion than during saline infusion, indicating stimulation of 3-MG transport into intracellular spaces with insulin. The 3-MG data were analyzed using a comprehensive model separately describing extracellular distribution and cellular transport of 3-MG by incorporating information on extracellular distribution kinetics obtained from L-glucose data. The combined L-glucose and 3-MG kinetic analysis precisely estimated insulin's effect in vivo to stimulate glucose transport into and out of intracellular spaces. We conclude that 1) insulin does not affect extracellular glucose distribution kinetics or volumes in conscious rats and 2) insulin's effects on cellular glucose transport in vivo can be assessed by simultaneous analysis of plasma L-glucose and 3-MG kinetics.


1969 ◽  
Vol 21 (03) ◽  
pp. 580-593
Author(s):  
L. A Pálos ◽  
G Sas ◽  
A Csurgay

SummaryThe reaction kinetics of the second phase of blood clotting (conversion of fibrinogen to fibrin) has been studied in euglobulin and thrombin-antithrombin systems. It was intended to set up relationships that would make mathematical expression of the processes possible and which would, moreover, help in detecting dynamic and functional relationships characteristic of the mechanism involved in coagulation.The experiments have yielded the following results:1. In the euglobulin solution containing no antithrombin the fibrinogen-thrombin reaction can be characterized with a constant deviation from the first order kinetics.2. The process of thrombin inactivation is a reaction of first order in the initial phase.3. The two basic processes (clotting by thrombin in euglobulin solution, inactivation of thrombin in defibrinated plasma) make it possible to predetermine the thrombin time of citrated plasma. Theoretical and actual clotting times were in good agreement.4. The thrombin time of plasma can be computed even if thrombin is not introduced to the system at one stride but gradually, a manner of administration which is a better imitation of what happening in vivo. 5. In connection with the computation of the “thrombin time” of citrated blood, we determined experimentally (and expressed by means of a function) the modification produced by the corpuscular elements of the blood in the reaction between fibrinogen and thrombin under atraumatic conditions.


1996 ◽  
Vol 270 (2) ◽  
pp. L183-L190 ◽  
Author(s):  
G. Saumon ◽  
G. Martet ◽  
P. Loiseau

The glucose concentration in the epithelial lining fluid (ELF) results from a balance between cellular uptake and paracellular leakage. The present study examines whether the ELF glucose concentration can be predicted from the kinetics of glucose transport obtained in fluid-filled lungs. Isolated rat lungs were filled via the trachea with instillate containing 0-10 mM glucose; the perfusate glucose concentration was 10 mM. The rate of glucose removal from airspaces depended on luminal glucose concentration and was saturable [maximum uptake rate = 101 +/- 8.6 mumol.h-1.g dry lung wt-1; apparent Michaelis constant K(m) = 1.5 +/- 0.43 mM; R2 = 0.79]. Glucose removal was inhibited by phloridzin but not by phloretin or by inhibiting glycolysis. The steady-state concentration in fluid-filled lungs was estimated to be 0.15 +/- 0.034 mM. It agreed with that (< 1/20 plasma) calculated using glucose transport kinetics and paracellular permeability. The ELF glucose concentration obtained by bronchoalveolar lavage was 0.39 +/- 0.012 plasma in vivo and 0.39 +/- 0.021 perfusate in air-filled isolated lungs. The equilibrium ELF/perfusate distribution ratio of alpha-methyl-glucose was similar to that of glucose. Thus there is a major difference between the alveolar steady-state glucose concentration in air- and fluid-filled lungs despite similar mechanisms of airspace glucose removal. This suggests that glucose kinetics or access to uptake sites differ in air- and fluid-filled lungs.


2002 ◽  
Vol 22 (19) ◽  
pp. 6706-6718 ◽  
Author(s):  
A. Audibert ◽  
D. Weil ◽  
F. Dautry

ABSTRACT The kinetics of pre-mRNA processing in living cells is poorly known, preventing a detailed analysis of the regulation of these reactions. Using tetracycline-regulated promoters we performed, during a transcriptional induction, a complete analysis of the maturation of two cellular mRNAs, those for LT-α and β-globin. In both cases, splicing was appropriately described by first-order reactions with corresponding half-lives ranging between 0.4 and 7.5 min, depending on the intron. Transport also behaved as a first-order reaction during the early phase of β-globin expression, with a nuclear dwelling time of 4 min. At a later time, analysis was prevented by the progressive accumulation within the nucleus of mature mRNA not directly involved in export. Our results further establish for these genes that (i) splicing components are never limiting, even when expression is induced in naive cells, (ii) there is no significant RNA degradation during splicing and transport, and (iii) precursor-to-product ratios at steady state can be used for the determination of splicing rates. Finally, the comparison between the kinetics of splicing during transcriptional induction and during transcriptional shutoff reveals a novel coupling between transcription and splicing.


1974 ◽  
Vol 65 (2) ◽  
pp. 368-372 ◽  
Author(s):  
A. Lorris Betz ◽  
David D. Gilboe

2007 ◽  
Vol 293 (6) ◽  
pp. E1782-E1788 ◽  
Author(s):  
Edward B. Arias ◽  
Gregory D. Cartee

In vivo calorie restriction [CR; consuming 60% of ad libitum (AL) intake] induces elevated insulin-stimulated glucose transport (GT) in skeletal muscle. The mechanisms triggering this adaptation are unknown. The aim of this study was to determine whether physiological reductions in extracellular glucose and/or insulin, similar to those found with in vivo CR, were sufficient to elevate GT in isolated muscles. Epitrochlearis muscles dissected from rats were incubated for 24 h in media with glucose (8 mM) and insulin (80 μU/ml) at levels similar to plasma values of AL-fed rats and compared with muscles incubated with glucose (5.5 mM) and/or insulin (20 μU/ml) at levels similar to plasma values of CR rats. Muscles incubated with CR levels of glucose and insulin for 24 h had a subsequently greater ( P < 0.005) GT with 80 μU/ml insulin and 8 mM [3H]-3- O-methylglucose but unchanged GT without insulin. Reducing only glucose or insulin for 24 h or both glucose and insulin for 6 h did not induce altered GT. Increased GT after 24-h incubation with CR levels of glucose and insulin was not attributable to increased insulin receptor tyrosine phosphorylation, Akt serine phosphorylation, or Akt substrate of 160 kDa phosphorylation. Nor did 24-h incubation with CR levels of glucose and insulin alter the abundance of insulin receptor, insulin receptor substrate-1, GLUT1, or GLUT4 proteins. These results provide the proof of principle that reductions in extracellular glucose and insulin, similar to in vivo CR, are sufficient to induce an increase in insulin-stimulated glucose transport comparable to the increase found with in vivo CR.


1985 ◽  
Vol 86 (1) ◽  
pp. 135-165 ◽  
Author(s):  
M Mahler

In frog sartorius muscle, after a tetanus at 20 degrees C, during which an impulse-like increase occurs in the rate of ATP hydrolysis, the rate of O2 consumption (QO2) reaches a peak relatively quickly and then declines monoexponentially, with a time constant not dependent on the tetanus duration (tau = 2.6 min in Rana pipiens and 2.1 min in Rana temporaria). To a good approximation, these kinetics are those of a first-order impulse response, and the scheme of reactions that couple O2 consumption to extramitochondrial ATP hydrolysis thus behaves as a first-order system. It is first deduced and then demonstrated directly that while QO2(t) is monoexponential, it changes in parallel with the levels of creatine and phosphorylcreatine, with proportionality constants +/- 1/tau p, where p is the P/O2 ratio in vivo. From this, it is further deduced that the mitochondrial creatine kinase (CK) reaction is pseudo-first order in vivo. The relationship between [creatine] and QO2 predicted by published models of the control of respiration is markedly different from that actually observed. As shown here, the first-order kinetics of QO2 are consistent with the hypothesis that respiration is rate-limited by the mitochondrial CK reaction; this has as a corollary the "creatine shuttle" hypothesis.


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