How the house sparrow Passer domesticus absorbs glucose
1 Department of Zoology, University of Wisconsin-Madison, USA
2 Department of Wildlife Ecology, 221 Russell Labs, 1630 Linden Drive,
University of Wisconsin-Madison, Madison, WI 53706, USA
* Author for correspondence (e-mail: wkarasov{at}wisc.edu)
Accepted 18 June 2004
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Summary |
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Key words: D-glucose, 3-O-methyl-D-glucose mediated absorption, passive absorption, house sparrow, Passer domesticus
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Introduction |
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Pappenheimer and colleagues
(Pappenheimer and Reiss, 1987;
Pappenheimer, 1990
) suggested
that the intestine's capacity to absorb glucose by mediated pathways is
inadequate to meet the daily intake of glucose and that most absorption occurs
by solvent drag across intestinal tight junctions (paracellular absorption),
secondary to active sugar and amino acid transport. In in vivo
experiments, a number of wild avian species achieved nearly complete
absorption of ingested L-glucose, the stereoisomer of
D-glucose that does not interact with the intestine's glucose
transporters and can only be absorbed passively
(Chang et al., 2004
): in
nectarivorous rainbow lorikeets, 80%
(Karasov and Cork, 1994
);
granivorous house sparrows, 80%
(Caviedes-Vidal and Karasov,
1996
); and omnivorous yellow-rumped warblers, 91%
(Afik et al., 1997
). These
findings in birds with diverse diet and taxonomic associations suggest that,
in birds, passive absorption is important for nutrient intake. However,
Schwartz et al. (1995
) pointed
out that L-glucose might be absorbed at a much slower rate than
D-glucose, but over the entire length of the intestine and the
extended time of digesta residence in the gut, its absorption could still be
fairly complete. Many birds have intestine lengths and digesta residence times
that are relatively short, not long
(Karasov and Levey, 1990
),
however, so how could birds exhibit nearly complete glucose absorption with
low rates of mediated and passive uptake?
An elegant approach to resolving this issue has been to compare the extent
and/or rate of absorption of L-glucose (absorbed only passively)
vs D-glucose or its analogue (absorbed actively and
passively) simultaneously in intact animals. In laboratory rats, the
absorption rate of the nonmetabolizable, actively transported
3-O-methyl-D-glucose apparently exceeded that of
L-glucose by about 9:1, implying that most glucose was absorbed
actively (Uhing and Kimura,
1995). Similar conclusions have been drawn for dogs
(Lane et al., 1999
) and humans
(Fine et al., 1993
). In this
study, we report the first measurements of this kind in an avian species, and
the findings are very different from those in the mammals studied so far.
Based on the earlier findings in birds, we predicted that passive
absorption must be important to glucose absorption, and we applied a
pharmacokinetic method focusing on appearance of radiolabeled
3-O-methyl-D-glucose (3OMD-glucose) and
L-glucose in blood to measure absorption in intact birds. Both of
these compounds are metabolically inert, which removes the possibly
confounding factor of post-absorptive catabolism from the analysis, but only
the former is transported by mediated processes at the brush border of house
sparrows (Chang et al., 2004)
and at the basolateral membrane (Kimmich,
1981
; Burant and Bell,
1992
). If mediated absorption is relatively most important, then
this will be apparent in slower absorption of L-glucose over an
extended period of time, relative to 3OMD-glucose. Alternatively, if the
majority of glucose is absorbed passively, then the absorption of the
radiolabeled 3OMD-glucose and L-glucose will be similar
in rate and extent (Fig.
1).
|
Because of uncertainty about normal luminal nutrient concentrations
(Ferraris et al., 1990;
Pappenheimer, 1993
), and how
they might influence the comparisons between the radiolabeled compounds, we
took measurements under substrate conditions that were both nonsaturating and
relatively more saturating for SGLT1, whose half-saturation glucose
concentration (apparent Km) is 5 mmol l-1
(Caviedes-Vidal and Karasov,
1996
). Also, we point out at the outset that in our comparison,
3OMD-glucose is handicapped relative to L-glucose for
several reasons. First, the molecular mass of 3OMD-glucose (194.2
Da) is greater than that of L-glucose (180.2 Da), which lowers its
diffusion coefficient in water and may decrease its rate of permeation,
relative to L-glucose, through the paracellular space, which
discriminates according to molecular size
(Chediack et al., 2003
). Also,
the affinity of the glucose transporters for 3OMD-glucose is lower
than for D-glucose (Kimmich,
1981
; Ikeda et al.,
1989
), so the former is an imperfect substitute for the latter. To
evaluate the implications of these differences, and other assumptions, on our
conclusions, we utilize a simulation model in conjunction with our
results.
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Materials and methods |
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Measurement of L-glucose and 3OMD-glucose absorption in vivo
Food was removed from birds overnight prior to an experiment, when these
diurnal birds would not normally eat, and measurements began 2.5-3 h after
lights went on in the morning. When measuring absorption under conditions
relatively nonsaturating for SGLT1, seven house sparrows were gavaged with 500
µl of a solution containing 200 mmol l-1 mannitol, 10 µCi
[14C]L-glucose and 20 µCi
[3H]3OMD-glucose (American Radiolabeled Chemicals St
Louis, MO, USA), and 80 mmol l-1 NaCl. When measuring absorption
under relatively saturating conditions, the mannitol was replaced with 200
mmol l-1 3OMD-glucose (N=6). To determine
elimination rate for absorption calculations, these same individuals were
injected into the pectoralis on other days with
[14C]L-glucose and
[3H]3OMD-glucose (5xµCi and 10 µCi,
respectively, in 250 µl 200 mmol l-1 mannitol and 80 mmol
l-1 NaCl). The sequence of trials was random, and repeated measures
on individuals were performed after intervals of at least 7 days, easily
enough time for residual radioactivity to return to background (normally less
than 24 h; see Results). The total osmotic pressure of gavage or injection
solutions was controlled at 360 mOsm with 5% variation (tested using a vapor
pressure osmometer; Wescor vapor 5502, Logan, UT, USA) so that solutions were
isosmotic with avian blood, and aliquot samples were saved for radioactivity
analysis. Following either gavage or injection, 7-9 blood samples (20 µl
each; total volume collected was <10% of blood volume in normal house
sparrows; Stangel, 1986) were
collected from the brachial vein with heparinized capillary tubes over the
next 3-4 h. Immediately after collection, blood was centrifuged (1500
g) for 5 min, plasma was separated and weighed
(10-20±0.1 mg), then mixed with 2.0 ml of scintillation fluor
(Hionic-Fluor, Packard, USA) and counted in a scintillation spectrometer
(Tracor Analytic, MarkIII, USA) for disintegrations per minute (d.p.m.) with
automatic external standardization (AES) and background correction
(Caviedes-Vidal and Karasov,
1996
).
In order to test for radiopurity, plasma samples from three different birds gavaged with different radioactive solutions were collected and analyzed along with three aliquot samples from each radioactive solution. Radiopurity was checked by high performance liquid chromatography (HPLC) using an NH3 column (Alltech, USA) with an acetonitrile:water (85:15%) mobile phase. All 3H activity was associated with 3OMD-glucose in the solution (92%) and in plasma (91%) and all 14C activity was associated with L-glucose in the solution (97%) and in plasma (93%). We also checked and found in preliminary injection and gavage experiments (not shown) that we obtained similar results for absorption of L- and 3OMD-glucose regardless of whether the 14C and 3H labels were on L-glucose or 3OMD-glucose.
Pharmacokinetic calculations
The radioactivity in each plasma sample at time t was normalized
to the mass of each sample (Ct, dpm mg-1
plasma) and plotted against sampling time. The integration of the area under
this curve (AUCt) represents the amount of radiolabeled probe that
has been absorbed from time 0 up to time t, whereas
AUCtotal denotes the total amount of probe absorbed from 0 up to
infinity time (). Following typical procedures in pharmacokinetics
(Gibaldi and Perrier, 1982
),
the area from t=0 to t=x min (when the final blood
sample was taken) was calculated using the trapezoidal rule. The area from
t=x min to t=
was calculated as
AUCx
=Ct (at
t=x)/Kel, where Kel is the
elimination rate constant, which can be determined for each bird in each
experiment based on the terminal portion of its absorption curve. The total
AUC0
was obtained by summing the two areas. Fractional
absorption (F), or bioavailability, for each probe was estimated
based on the ratio between the area under the probe plasma concentration
versus time curve for oral gavage experiments (AUCoral, in
units of d.p.m. min g-1 plasma) and injection experiments
(AUCinj) normalized to the respective dosage given to the animal:
![]() | (1) |
This method of calculating F is favored because it makes no major assumptions about compartments or kinetics. Fractional absorption estimates how much of the gavaged probe was absorbed into the animal's system.
Additional analyses relating to the time course and apparent rate of
absorption were made assuming an open two-compartment model and first order
elimination. A two-compartment model was selected following inspection of the
curves of Ct vs sampling time post-injection (see
Results). In 20 out of 26 cases, a bi-exponential elimination model fit the
data significantly better (P<0.05) than a mono-exponential model,
using an F-test (Motulsky and
Ransnas, 1987). For each individual, parameters for the
biexponential model were derived by the curve-stripping method
(Gibaldi and Perrier, 1982
):
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In the two-compartment model, rate constants and distribution spaces are
derived from the constants A, B, and ß. For example, the
elimination rate constant of the probe from the apparent central compartment,
to which we will refer later, is estimated as (A+B)/[(A/
)+(B/ß)].
The rate constants and spaces are used in conjunction with the data from
gavage experiments to calculate the cumulative proportion of F that
was absorbed at each blood sampling time point (Pt),
according to the Loo-Riegelman method
(Wagner, 1975
;
Gibaldi and Perrier, 1982
).
The true cumulative absorption at any sampling time point (t) is the
product of F and Pt, and the apparent absorption
rate during two adjacent sampling time points is
F
P/
t.
In the few cases where a mono-exponential model fit elimination best, or if
elimination data were not available because an injection experiment was not
performed (4 of 13 birds), we used the mean distribution space measured in
other birds and applied the one-compartment model
(Wagner, 1975) for calculating
F, P and apparent rates. As discussed by Wagner
(1975
), the two models can
yield very similar results under many circumstances, which we also found to be
the case (N=9). Also, fractional absorptions did not differ
significantly when estimated using a compartmental model versus the
compartment-independent method [e.g. for L-glucose respectively,
0.73±0.03 (mean ± S.E.M.) vs
0.72±0.04; P>0.6, N=9]. Although the
two-compartment model is more complex, we retained it when appropriate
because, theoretically, the two-compartment model would be better able to
detect experimental differences (Loo and
Riegelman, 1968
; Wagner,
1975
; Gibaldi and Perrier,
1982
). If there are some organs and tissues in an organism where
blood circulation is not as high as the rest of body, this may lead to a
higher concentration of probe in these peripheral compartment(s) compared to
the central compartment. Thus these poorly perfused peripheral compartments
can serve as another source for probes entering the central compartment,
secondary to an absorption site like the small intestine. In comparison to the
one-compartment model, a two-compartment model is more conservative in that it
provides corrections for the redistribution of probe from these peripheral
compartments (Gibaldi and Perrier,
1982
; Riviere,
1999
).
Statistical analysis
Numerical data are presented as means ± S.E.M.
(N=number of animals). Although data shown in the figures are mean
values, statistical analyses were performed based on data for individuals.
Fractional absorption (F) was arcsine square-root transformed before
statistical analysis. Results were analyzed by analysis of variance (ANOVA),
repeated-measures ANOVA, and Student's t-test (SAS, SAS Institute
Inc, Cary, NC, USA). The T- and F-values of these and other
ANOVAs are presented in the text with the relevant degrees of freedom as
subscripts. Linear regression was by the method of least squares. Nonlinear
curve fitting (Gauss-Newton algorithm, SYSTAT;
Wilkinson, 1992) was used to
fit kinetic data, and kinetic models were compared according to Motulsky and
Ransnas (1987
). Statistical
significance was accepted for P<0.05. One-tailed tests were used
for a priori predictions.
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Results |
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Information on the apparent rates of probe absorption was derived from plots of fractional absorption as a function of time (Fig. 4A,B). Apparent absorption rates declined with increasing time since gavage, and the rates were compared within the trials using a repeated-measures ANOVA. Under conditions relatively nonsaturating for SGLT1 (Fig. 4A), the least-squares adjusted mean absorption rate for 3OMD-glucose (1.91±0.15% absorbed min-1) significantly exceeded that for L-glucose absorption (1.63±0.14% absorbed min-1) by 17% (F1,62=4.01, P=0.049). Under relatively more saturating conditions (Fig. 4B), the apparent absorption rates of the two probes did not differ significantly (respectively, 2.59±0.38 vs 2.67±0.42% absorbed min-1; F1,45=0.1, P>0.7). Statistical comparison of these values across the treatments showed that apparent rate of absorption was significantly enhanced for the L-glucose probe by 57% (F1,52=24, P<0.01) and for the 3OMD-glucose probe by 36% (F1,55=8.28, P<0.001), when measured under conditions that were relatively more saturating for SGLT1.
|
Assuming that absorption of L-glucose is a proxy for passive absorption of 3OMD-glucose, whereas the absorption of 3OMD-glucose represents the sum of passive + mediated absorption, the ratio of the apparent absorption rates (L/D) indicates the proportion of 3OMD-glucose absorption that occurs via the passive pathway. Accordingly, we plotted this ratio over the course of the trials (Fig. 5). The ratio always exceeded 0.7, with no significant difference between treatments. This suggests that more than 70% of 3OMD-glucose absorption probably occurred via the passive pathway, regardless of whether the measures were made under conditions relatively nonsaturating or relatively saturating for SGLT1. However, the following discussion revisits a number of assumptions upon which this conclusion is based.
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Discussion |
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The majority of 3OMD-glucose absorption is via a passive route in house sparrows
If 3OMD-glucose is mainly actively absorbed by the intestine,
then a much higher rate of absorption of
[3H]3OMD-glucose than of
[14C]L-glucose is predicted. For example, if 95% of the
instantaneous glucose absorption is active, as suggested in some studies
(Uhing and Kimura, 1995;
Fine et al., 1993
;
Lane et al., 1999
), and if
3OMD-glucose is a good proxy for D-glucose, then the ratio of the
absorption rate for L-glucose to 3OMD-glucose should be
about 0.05. However, we found similar fractional absorption and apparent rates
of absorption for L- and 3OMD-glucose in house sparrows
(Fig. 4) and the ratio never
fell below 0.7 (Fig. 5),
indicating >70% passive absorption of glucose.
Schwartz et al. (1995) made
the point that simply comparing F for 3OMD- and
L-glucose might be misleading. Suppose that 3OMD-glucose
is absorbed at a high rate in the proximal portion of the intestine, whereas
L-glucose is absorbed at a very slow rate. The fractional
absorption of L-glucose could still be fairly complete if its slow
absorption occurred over the entire length of the intestine and over the
entire time of digesta residence. We do not think that this explanation
applies to the house sparrows. Absorption of L-glucose did not seem
prolonged compared with that for D-glucose (insets in
Fig. 4). 3OMD- and
L-glucose had apparent absorption rates similar to each other
throughout all the sampling time points
(Fig. 4). When measurements
were done under conditions relatively nonsaturating for SGLT1, even for the
largest difference at 10 min after gavage the apparent absorption rate of
3OMD-glucose was only 1.32-times higher than that of
L-glucose. When measurements were done under more saturating
conditions, the fractional absorption of L-glucose was the same as
that for 30MD-glucose, the apparent absorption rate of
3OMD- and L-glucose followed each other closely
throughout the course of experiment, and the mean apparent absorption rates
were not statistically different from each other either.
In the Introduction we suggested that in the comparison of 3OMD-
and L-glucose, the former was handicapped relative to the latter
for several reasons. First, we previously found that the fractional absorption
of carbohydrates absorbed passively by the house sparrow declines with
increasing molecular mass (MW) of the probe, by an average of -0.002
Da-1 (Chediack et al.,
2003). The reasons for this probably include the fact that
diffusion coefficients decline with increasing MW1/2, and the
paracellular space discriminates according to molecular size, much like a
sieve (Chang et al., 1975
;
Friedman, 1987
). Considering
the 14 Da difference in the molecular mass of L-glucose and
3OMD-glucose, the direct comparison of their fractional absorptions
(averaging, respectively, 0.73 and 0.76) might be adjusted by increasing the
value for 3OMD-glucose by 0.03 (i.e. the product of 14 Da and 0.002
Da-1). This would not change the overall conclusion that their
extent and rate of absorption are very similar when measured
simultaneously.
The affinities of both the brush border and basolateral glucose
transporter(s) are lower for 3OMD-glucose than for
D-glucose (Kimmich,
1981; Ikeda et al.,
1989
), so the former is an imperfect substitute for the latter. To
evaluate the implications of this difference for our conclusions, we utilized
a simulation model of absorption by mediated and passive pathways that we
discuss in the next section. Thinking about how the
[3H]3OMD-glucose interacted with a glucose transporter
also helped to highlight what was notable about our second major empirical
finding - that the rates of absorption increased, even for
[3H]3OMD-glucose, when the measurements were done under
conditions relatively more saturating for the glucose transporter.
Simulation of sugar absorption supports the interpretation of empirical findings
In order to characterize absorption of D-, L- and
3OMD-glucose in intact animals, we constructed a model for
absorption at the apical membrane using idealized simple reactor theory,
following the approach of Penry and Jumars
(1987), who proposed that
tubular organs such as the intestine are analogous to plug-flow reactors in
chemical engineering. In a plug-flow reactor, material is mixed
instantaneously and continuously in the radial direction without appreciable
axial mixing, and items leave the tube in the same order that they entered. At
low and high substrate concentrations, we simulated several possible patterns
of 3OMD-glucose absorption, including expected patterns if mediated
absorption were dominant, but with different apparent affinities between the
transporter and its substrate, and an expected pattern in the event that
passive absorption were dominant. We used the results as a check on our
conclusions based on empirical results.
Nonsaturable absorption
The simplest case when modeling the kinetics of nutrient absorption is for
an animal absorbing food entirely through passive, nonsaturable process(es).
In the plug-flow reactor-like intestine of the animal eating hexoses
(requiring no hydolysis), the only reaction is absorption, and its rate of
removal of substrate from the reactor is -rL in nmol
µl-1 min-1
(Jumars and Martinez del Rio,
1999). Note that here, and elsewhere, rates are normalized to the
reactor volume, which has units of µl. The luminal or gut volume was
estimated assuming a tube with an averaged small intestinal (SI) length equal
to 18.3 cm and SI luminal radius of 0.1 cm
(Caviedes-Vidal and Karasov,
1996
). The passive absorption is determined by the absorption rate
constant, Ka (min-1), and substrate
concentration Ct (nmol µl-1) at the reaction
or absorption site at time t:
![]() | (3) |
Paracellular absorption of hydrosoluble molecules across small intestinal
mucosal epithelium is best described in the context of the Kedem-Katchalsky
equation (Kedem and Katchalsky,
1958), which includes the contribution of both diffusion and
solvent drag to the flux of solutes through porous epithelia.
Ka is thus a lumped first-order coefficient of both
diffusion and solvent drag flux, which both occur in linear proportion to
substrate concentration Ct.
Mediated plus nonsaturable absorption
Carrier-mediated process(es) can be assumed to have Michaelis-Menten
kinetics with a Michaelis constant (Km, in nmol
µl-1) reciprocally related to the affinity of the carrier system
for the substrate and a rate of removal of substrate from the reactor
(Vmax, nmol µl-1 min-1) at
saturating substrate concentration. The rate of intestinal absorption of a
single hexose, such as 3OMD-glucose, by both mediated and
nonsaturable processes (-rD), can thus be calculated
following the approach of Dade et al.
(1990):
![]() | (4) |
Modeling for probe absorption
The kinetics of probe absorption is the final target for this modeling
exercise because radiolabeled probe was the measurable parameter in our
studies. 14C-labeled L-glucose probe presumably behaves
like a nonsaturable substrate, thus its absorption is described by Equation 3.
However, the absorption of [3H]3OMD-glucose probe, which
includes mediated plus nonsaturable absorption, is more complicated.
[3H]3OMD-glucose probe will compete with labeled and
unlabeled substrate for the reaction sites or transporters in the small
intestine (Malo and Berteloot,
1991). Because 3OMD-glucose can be absorbed by both
passive and mediated routes, the absorption rate of
[3H]3OMD-glucose probe (-rDP) at the
absorption site can be estimated as follows:
![]() | (5) |
Here, CDPt is the 3OMD-glucose probe concentration (nmol µl-1) at time t at the absorption site. Luminal unlabeled 3OMD-glucose concentration at time t (CCt) can be described by Equation 4 with any given initial concentration at time zero.
In the simulation, the reaction or absorption rate at time t is calculated by formulae as described above with any given initial substrate concentrations. Assuming that the volume of gut contents does not change with time and that the absorption rates stay unchanged from time t to time t+1, the absorption rate times the intestine luminal volume approximates how much substrate is absorbed during the time interval. By subtracting this value from the initial total substrate content at time t, the initial substrate concentration at time t+1 can be calculated from the remainder. With this initial substrate concentration at time t+1, the subsequent absorption rate and the amount of absorption during the next time interval can also be calculated following the same rule. Plotting the values gathered from a simulation run from t=0 to t=50 min, when most absorption had occurred in theory and in fact (Fig. 4A,B), we estimated the relative rate and extent of [14C]L-glucose and [3H]3OMD-glucose absorption. The selection of initial parameter values is described in the legend of Fig. 6.
|
Results of simulations
The simulated cumulative absorption (Figs
6A,
7A) and apparent rate of
absorption (Figs 6B,
7B) of radiolabeled
3OMD-glucose are considerably greater than that of radiolabeled
L-glucose in all the situations modeled (i.e. Figs
6Ai-iii,Bi-iii,
7Ai-iii,Bi-iii), except when
the apparent passive permeability coefficient was increased (compare Figs
6Aiv,Biv,
7Aiv,Biv with all other
panels). Adjusting upward the apparent Km for mediated
3OMD-glucose absorption (Figs
6Aii,
7Bii) had little effect on this
comparison. The predicted rates of probe absorption were in most cases
depressed in the presence of high luminal D-glucose concentration
(c.f. Figs 6B,
7B), as might be expected
because the labeled probe competes with non-labeled substrate for uptake from
the lumen. The one situation in which high luminal substrate concentration had
little effect on predicted probe absorption rate was when the apparent passive
permeability coefficient was increased, and this makes sense because most of
the predicted probe absorption is nonmediated and thus not competitively
inhibited.
|
The simulation results support our interpretation of the empirical results, and they add one new insight. First, simulation results are consistent with the empirical findings that absorption by intact house sparrows was not dominated by the mediated pathway. The simulations indicate that when passive absorption dominates, then absorption of 3OMD- and L-glucose will be similar in rate and extent (see especially Figs 6Aiv,Biv, 7Aiv,Biv), which is what we observed empirically (Fig. 4). In contrast, the simulations indicate that if mediated absorption had dominated, then the absorption of 3OMD-glucose should have been more rapid and extensive than that of the L-glucose, even despite the fact that the 3OMD-glucose has a lower affinity than D-glucose for the brush border glucose transporter (see especially Figs 6Aiii,Biii, 7Aiii,Biii), but this was not observed empirically.
Second, the simulations help us interpret a second empirical finding - that
when the measurements were done under conditions relatively more saturating
for the glucose transporter, the rates of absorption increased, even for
[3H]3OMD-glucose (c.f.
Fig. 4A,B). In contrast to this
empirical finding, the simulation indicated that if most
[3H]3OMD-glucose uptake were mediated, then its
absorption would have been inhibited by unlabeled substrate in the lumen
rather than accelerated. However, studies in mammals
(Pappenheimer and Reiss, 1987;
Madara and Pappenheimer, 1987
;
Pappenheimer, 1987
;
Pappenheimer and Volpp, 1992
;
Sadowski and Meddings, 1993
;
See and Bass, 1993
;
Turner and Madara, 1995
;
Chang et al., 2004
) and in
birds (Chediack et al., 2003
)
have shown that hydrophilic molecules cross the intestinal mucosa by diffusion
and/or solvent drag via a paracellular pathway, and that the
permeability of this pathway is enhanced when Na+-coupled nutrient
transport occurs. The mechanism(s) for acceleration by luminal glucose is not
known in house sparrows, but might be increased solvent drag and/or
cytoskeletal contractions (Madara and
Pappenheimer, 1987
;
Pappenheimer, 1987
; Madara et
al., 1986
,
1988
) or protein strand
alterations that alter the tight junction effective pore size
(Pappenheimer and Reiss,
1987
). This feature was not included in our simple simulation.
Mediated transport by SGLT1 seems to play a role in the acceleration of
passive absorption, because when the former was partially blocked by
phloridzin, the specific SGLT1 inhibitor, in vivo passive absorption
was reduced by about a third in laboratory rats
(Fasulo et al., 2001
).
Passive absorption and its ecological and evolutionary implications
Our results underscore how, in some animals, the glucose absorptive
capacity of the small intestine cannot be accurately estimated only on the
basis of in vitro measurements of mediated glucose uptake. The
quantitative determination of physiological capacity in relation to load has
been called a new research frontier
(Diamond, 1993), and our
research helps establish important limits on scientists' attempts to match the
capacity to absorb nutrients determined on the basis of in vitro data
with nutrient intake seen in vivo.
From an evolutionary perspective, one can argue that there are both costs
and benefits to intestinal permeability to hydrosoluble biochemicals. A
possible cost is that a high intestinal permeability that permits passive
absorption might be less selective than a carrier-mediated system for nutrient
absorption and might permit toxins to be absorbed from plant and animal
material in the intestinal lumen (Diamond,
1991). But it has also been suggested
(Pappenheimer, 1993
) that
passive absorption may confer a selective advantage because it requires little
energy and provides a mechanism whereby rate of absorption is matched to rate
of hydrolysis. Opposing costs and benefits could lead to variation among
species in intestinal permeability to hydrosoluble biochemicals. This could
explain why studies of some species indicate relatively low reliance on
passive absorption (Fine et al.,
1993
; Uhing and Kimura,
1995
; Schwartz et al.,
1995
; Lane et al.,
1999
) and others such as ours indicate relatively high reliance
(Pappenheimer, 1990
,
1998
;
Karasov and Cork, 1994
;
Karasov et al., 1996
;
Levey and Cipollini, 1996
).
For the latter type, vulnerability to hydrophilic toxins could be an important
ecological driving force, constraining food exploratory behavior, limiting the
breadth of the dietary niche, and selecting for compensatory behaviors such as
searching for and ingesting specific substances that inhibit hydrophilic toxin
absorption (Diamond et al.,
1999
).
To continue to advance knowledge on the nutritional, pharmacological, and ecological significance of paracellular absorption we need to determine in more species the relative importance of passive absorption with whole-animal studies like the present one and test different probes and different putative modulators of the paracellular pathway.
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Acknowledgments |
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References |
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