Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Medical School, Clinic, and Foundation, Rochester, Minnesota 55905
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ABSTRACT |
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The physiological relevance of the
absorption of glucose from bile by cholangiocytes remains unclear. The
aim of this study was to test the hypothesis that absorbed glucose
drives aquaporin (AQP)-mediated water transport by biliary epithelia
and is thus involved in ductal bile formation. Glucose absorption and
water transport by biliary epithelia were studied in vitro by
microperfusing intrahepatic bile duct units (IBDUs) isolated from rat
liver. In a separate set of in vivo experiments, bile flow and
absorption of biliary glucose were measured after intraportal infusion
of D-glucose or phlorizin. IBDUs absorbed
D-glucose in a dose- and phlorizin-dependent manner with an
absorption maximum of 92.8 ± 6.2 pmol · min1 · mm
1.
Absorption of D-glucose by microperfused IBDUs resulted in
an increase of water absorption (Jv = 3
10
nl · min
1 · mm
1,
Pf = 40 × 10
3 cm/sec).
Glucose-driven water absorption by IBDUs was inhibited by
HgCl2, suggesting that water passively follows
absorbed D-glucose mainly transcellularly via
mercury-sensitive AQPs. In vivo studies showed that as the amount of
absorbed biliary glucose increased after intraportal infusion of
D-glucose, bile flow decreased. In contrast, as the
absorption of biliary glucose decreased after phlorizin, bile flow
increased. Results support the hypothesis that the physiological
significance of the absorption of biliary glucose by cholangiocytes is
likely related to regulation of ductal bile formation.
liver; cholangiocytes; absorption; secretion; aquaporins; phlorizin; microperfusion; intrahepatic bile duct units
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INTRODUCTION |
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IT HAS BEEN KNOWN FOR
YEARS (12) that the basal concentration of glucose
in hepatic bile is extremely low (i.e., 0, <1.0 mM) compared with
plasma (i.e., >5.0 mM). Earlier elegant studies explored blood-bile
glucose concentration differences and provided convincing evidence that
glucose enters canalicular bile in equal concentration to plasma and
then is subsequently reabsorbed from bile by the intrahepatic bile
ducts by sodium-dependent and sodium-independent transport mechanisms
(12, 16, 25). Recently, we extended these studies
employing confluent, polarized monolayers of rat cholangiocytes and
demonstrated that cholangiocytes express a sodium-dependent glucose
transporter, SGLT1, at their apical plasma membrane and a facilitative
glucose transporter, GLUT1, at their basolateral plasma membrane
domain. We proposed that these two proteins accounted for the vectorial
(i.e., from bile to blood) transport of glucose and that their
coordinated activities provided a plausible explanation for the low
concentration of glucose in bile (15).
Nevertheless, the physiological relevance of glucose absorption from bile by cholangiocytes remains unclear, although at least two possibilities have been offered. It was suggested that absorption of biliary glucose contributes to the sterility of bile by removing a potential microbial nutrient (16). Alternatively, we proposed that absorption of biliary glucose by cholangiocytes would induce water absorption by biliary epithelia because glucose would act as an osmolyte in the biliary tree (15). However, direct exploration of this second hypothesis was not possible because an appropriate experimental approach was unavailable until now. Recently, we developed and characterized a novel experimental model, the microperfused rat intrahepatic bile duct unit (IBDU); this model allows direct measurement of ion, solute, and water transport across biliary epithelia (19). In the study described here, we applied this model to complement in vivo experiments to test the hypothesis that glucose absorbed from bile by cholangiocytes drives water absorption by the biliary epithelia and, thus, is involved in ductal bile formation.
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MATERIALS AND METHODS |
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Materials. All chemicals were of the highest purity commercially available and were purchased from Sigma Chemical (St. Louis, MO) unless otherwise indicated. Fluorescein sulfonate [FS, fluorescein-5(6)-sulfonic acid, trisodium salt] was obtained from Molecular Probes (Eugene, OR).
Animals. Male Fisher 344 rats (225-250 g) were obtained from Harlan Sprague Dawley (Indianapolis, IN), housed in a temperature-controlled room (22°C) with 12:12-h light-dark cycles, and maintained on a standard diet with free access to water. All experimental procedures were approved by the Animal Use and Care Committee of the Mayo Foundation.
Solutions. The composition of standard Ringer-HCO3 buffer (KRB) was (in mM) 120.0 NaCl, 5.9 KCl, 1.2 Na2HPO4, 1.0 MgSO4, 25.0 NaHCO3, 1.25 CaCl2, and 5.0 D-glucose. The concentration of D-glucose in KRB perfused through the lumen of IBDUs was varied from 0 to 30 mM; the bathing KRB contained corresponding concentrations of sucrose. The precise osmolality of KRB solutions was determined with a freezing point osmometer (Advanced Micro-Osmometer, model 3300; Advanced Instruments, Norwood, MA).
Microperfusion of isolated rat IBDUs in vitro. IBDUs, which are pieces of intrahepatic bile ducts ranging in luminal diameter from 100 to 125 µm and in length from 1.0 to 1.5 mm, were isolated from normal rat liver and perfused as previously described in detail (19). Briefly, individual isolated IBDUs were placed in a specially designed, temperature-controlled chamber mounted on the stage of an inverted fluorescence microscope (Nikon, eclipse, TE300). Concentric glass pipettes were used to position and perfuse the IBDUs at a rate of 40 nl/min. The system was checked for potential leakage by using trypan blue dye or FS. The bath solution was changed during the experiment with an exchange rate of 1.0-1.5 ml/min. The perfused IBDUs were allowed to equilibrate for 30 min before the experimental protocol was started; their viability was assessed by trypan blue exclusion.
Measurement of D-glucose absorption. IBDUs were perfused with KRB containing physiologically relevant concentrations of D-glucose (i.e., 5, 10, and 15 mM). In addition, IBDUs were perfused with 30 mM D-glucose to determine a biliary glucose absorption maximum, BmG. At 30-min intervals, the collected fluid was removed by a sampling pipette, and D-glucose concentration in timed samples was determined with a biochemistry analyzer (YSI 2700 Select; Yellow Springs Instrument, Yellow Springs, OH). Absorption of D-glucose by microperfused IBDUs was calculated from the concentrations of D-glucose in the perfused and collected solutions, the time of perfusion, and the length of IBDUs and was given in picomoles per minute per millimeter. To study the effects on D-glucose absorption by cholangiocytes of a specific inhibitor of SGLT1, phlorizin, and a sulfydryl reagent, HgCl2, that blocks water channels, IBDUs were perfused with KRB containing 15 mM D-glucose and 0.5 mM phlorizin or with KRB containing 15 mM D-glucose and 0.3 mM HgCl2, respectively.
Measurement of water movement across intrahepatic biliary
epithelia.
IBDUs were perfused with KRB containing both the impermeable
fluorescent volume marker FS (1 mM) and different concentrations (0, 5, 10, 15, and 30 mM) of D-glucose. FS fluorescence was
detected from 50-µm-diameter circular spots at the proximal and
distal ends of IBDUs by a photosensor module (H5784; Hamamatsu
Phototonics, Bridgewater, NJ), as previously described in detail
(19). Net water movement (Jv) was
calculated from the perfusion rate and the initial (CO) and
collected (CL) osmolalities of the perfusate: Jv = VO/L(CL/CO 1),
where VO is the perfusion rate (in nl/min); L is
the length of bile duct unit studied (in mm); CL is the
osmolality of collected fluid; and CO is the
osmolality of the perfusate. CL was determined from the
product of CO and the ratio of fluorescence intensities at
the proximal and distal ends of microperfused IBDUs, as described
previously (14, 19). The transepithelial osmotic water
permeability coefficient, Pf (cm/s), was
calculated from the relation Pf = Jv/Vm · A ·
C,
where Jv is net water movement (in
cm3/s); Vm is partial molar volume of water (18 cm3/mol); A is the surface area of the lumen of
IBDUs (in cm2); and
C is the osmotic gradient (in
mol/cm3) (7). Jv,
CO, and CL were calculated as described above.
The osmotic gradient was calculated as
C = CL
CO. The luminal surface area A was calculated
as A =
/DL, where the inner diameter
D and the length L of IBDUs were determined by
using a calibrated eyepiece micrometer. To study the effects of
phlorizin and HgCl2 on transepithelial water transport,
IBDUs were perfused through their lumen with KRB containing 15 mM
D-glucose and 0.5 mM phlorizin or with KRB containing 15 mM
D-glucose and 0.3 mM HgCl2, respectively.
In vivo experiments. Rats were anesthetized with intraperitoneally injected nembutal (5 mg/100 g body wt); the common bile duct was cannulated above the pancreas with PE 10 intramedic polyethylene tubing (Clay-Adams, Parsippany, NJ), and glucose or phlorizin was infused into the portal vein through a 16-gauge intraveneous catheter (Becton Dickinson Infusion Therapy Systems, Sandy, UT) by using a microliter syringe pump (model 2274; Harvard Apparatus, Holliston, MA) with a Hamilton 5-ml gas-tight syringe. Infusions were maintained in all experiments at a rate of 60 µl/min to produce in portal blood the required final concentration of D-glucose (15 mM) or phlorizin (0.5 mM). The temperature of each rat was maintained at 37°C by Vetko thermal barrier and regulated through a rectal probe by Tele Thermometer YSI (Yellow Springs Instrument). Bile was collected every 10 min, and volume was determined gravimetrically by assuming a bile density of 1.0 g/ml. Bile flow was given in microliters per minute per gram of liver. The concentration (in mM) of glucose in plasma and bile and bile osmolality (mosM) were measured as described above. The amount of glucose absorbed (in mM) by intrahepatic bile ducts was estimated from the concentration of glucose in plasma and bile before and after intraportal infusion of D-glucose and phlorizin.
Statistical analysis. All values are expressed as means ± SE. Statistical analysis was performed by the Student's t -test, and results were considered statistically different at P < 0.05.
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RESULTS |
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Absorption of D-glucose by microperfused IBDUs.
Data presented in Fig. 1 show that
microperfusion of IBDUs with KRB containing different concentrations of
D-glucose results in absorption of D-glucose
from the perfusate with a biliary glucose absorption maximum
(D-glucose BmG) of 92.8 ± 6.2 pmol · min1 · mm
1. The
amount of absorbed D-glucose depended on the concentration of D-glucose in the perfusate and reached
D-glucose BmG when IBDUs were perfused with 15 mM D-glucose.
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Identification of mechanisms of D-glucose absorption by
microperfused IBDUs.
IBDUs were perfused with KRB containing 15 mM D-glucose and
phlorizin, a specific inhibitor of the sodium-dependent glucose transporter, SGLT1, expressed on the apical plasma membrane of cholangiocytes (15). Data in Fig.
2 show that phlorizin inhibited absorption of D-glucose in microperfused IBDUs by 85.6%,
indicating that intrahepatic biliary epithelia absorb
D-glucose mainly via SGLT1. HgCl2 also
inhibited absorption of D-glucose in microperfused IBDUs;
however, its inhibiting effect was limited because the absorption of
D-glucose was inhibited by only 24.5%.
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Water transport by microperfused IBDUs.
Initially, IBDUs were perfused through their lumen with FS, the
impermeable fluorescent volume marker, in glucose-free KRB. In this
experiment, FS fluorescence detected at the proximal and distal ends of
IBDUs was constant (Fig. 3). In contrast,
when IBDUs were perfused with 5, 10, and 15 mM D-glucose,
the FS fluorescence at the distal end of the IBDU increased, reflecting
water movement from lumen to bath, i.e., water absorption (as an
example, the original tracing of FS fluorescence in IBDU lumen perfused
with 15 mM D-glucose is shown in Fig. 3). However,
increasing luminal glucose concentration above the absorptive capacity
of SGLT1 (i.e., 30 mM) resulted in a decrease of luminal FS
fluorescence, reflecting water movement from bath to lumen, presumably
by increasing the osmotic gradient favoring secretion (Fig. 3). The
calculated Jv values suggest (Fig.
4) that water is absorbed by IBDUs
perfused with 5 to 15 mM of D-glucose with rates from 3 to
10 nl · min1 · mm
1.
Calculated Pf (
40 × 10
3
cm/s) values showed (Fig. 4) that water is absorbed by the biliary epithelia rapidly, suggesting that specific aquaporins (AQPs) may be
involved in this process. The absolute values of physical characteristics (i.e., Jv and
Pf) for water secretion in microperfused IBDUs
were similar to those observed for water absorption (Fig. 4).
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Identification of mechanisms of water transport by microperfused
IBDUs.
IBDUs were perfused with KRB containing 15 mM D-glucose and
a specific inhibitor of SGLT1, phlorizin, or with KRB containing 15 mM
D-glucose and an inhibitor of AQP, HgCl2. Data
in Fig. 5 show that both phlorizin and
HgCl2 decrease water absorption by IBDUs microperfused with
15 mM D-glucose by 75.5 and 68.9%, respectively. These
data, in conjunction with data demonstrating absorption of
D-glucose by IBDUs in the presence and absence of phlorizin and HgCl2 (Fig. 2), suggest that water follows actively
absorbed D-glucose passively mainly transcellularly with
mechanisms involving mercury-sensitive AQPs expressed on the
cholangiocyte apical plasma membrane.
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Biliary water absorption as a function of D-glucose
absorption in microperfused IBDUs.
Data presented in the Fig. 6 show that
absorption of D-glucose by microperfused IBDUs is
associated with a proportionate increase in water absorption. These
data, taken together with data demonstrating inhibition of
D-glucose and water absorption by phlorizin and HgCl2 (Figs. 2 and 5), suggest that D-glucose
absorbed by cholangiocytes drives water absorption by biliary
epithelia.
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Bile flow as a function of glucose absorption by intrahepatic bile
ducts in vivo.
D-Glucose and a specific inhibitor of SGLT1, phlorizin,
were infused into the portal vein to examine the effects of biliary glucose on bile secretion in vivo. Assuming that glucose
enters canalicular bile in concentrations equal to blood
concentrations, we estimated the amount of D-glucose
absorbed by intrahepatic bile ducts after intraportal infusion of
D-glucose and phlorizin and analyzed these data in
conjunction with bile flow (Table 1). These data, taken together, show that as the amount of absorbed biliary
glucose increased 2.6-fold after intraportal infusion of 15 mM
D-glucose, bile flow decreased 9.3%. In contrast, as the
absorption of biliary glucose decreased by 3.6-fold after phlorizin,
bile flow increased by 11.7%. Bile osmolality did not change after
infusion of D-glucose but increased after phlorizin (Table
1).
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DISCUSSION |
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The primary objective of this study was to define the physiological significance of the absorption of glucose from bile by intrahepatic bile ducts. Whereas a considerable body of evidence indicates that glucose stimulates absorption of water in a variety of transporting epithelia (2, 4, 10, 13, 23, 32), direct evidence for a specific effect of glucose on water transport in intrahepatic biliary epithelia is lacking.
We used both a novel experimental model, the microperfused rat IBDU,
which we recently developed (19), and a conventional in
vivo model to address this issue. The microperfused IBDU allowed us to
directly quantitate both glucose and water transport by the biliary
epithelia by perfusing the intrahepatic bile ducts with physiological
concentrations of D-glucose at rates that correspond to
basal intrahepatic bile flow in vivo (20). The basal
concentration of glucose in rat blood is 5-6 mM and might be
increased up to 20 mM under physiological and pathological conditions
(2, 11, 12). In contrast, concentrations of biliary
glucose never exceed 1-2 mM even in rats with experimental
diabetes (11, 12). These observations suggest that glucose
which enters canalicular bile at concentrations 5-20 mM is
effectively absorbed by cholangiocytes under normal and pathological
conditions. Using a microperfused IBDU model, we demonstrated that,
under physiological conditions, biliary epithelia absorb
D-glucose with a BmG of 92.8 ± 6.2 pmol · min1 · mm
1, a number
comparable to the glucose absorption maximum measured in the
microperfused proximal convoluted tubule (TmG) of the rat (51.8 ± 2.0 pmol · min
1 · mm
1) and
rabbit (78.5 ± 5.1 and 83.2 ± 5.1 pmol · min
1 · mm
1) kidney
(3, 8, 29).
The absorption of D-glucose by microperfused IBDUs was inhibited by phlorizin, suggesting that cholangiocytes absorb D-glucose mainly via SGLT1. This finding is consistent with our previous observation that isolated cholangiocytes absorb glucose mainly by this transporter (15) and with the observation that phlorizin also effectively inhibits glucose absorption by microperfused proximal convoluted kidney tubules (32). Absorption of D-glucose by microperfused IBDUs was also somewhat inhibited by HgCl2, possibly due to binding of HgCl2 to cysteine residues on SGLT1. However, that inhibition was not specific and was more limited than phlorizin inhibition of SGLT1.
A specific role for D-glucose on water transport by intrahepatic bile ducts is supported by our studies. The close correlation between glucose and water absorption by microperfused IBDUs and our finding that biliary absorption of water is inhibited by phlorizin suggest that absorbed D-glucose drives water transport in cholangiocytes.
Thus our findings here, taken together with previous observations regarding the expression of SGLT1 and AQP1 in both the proximal tubule of the kidney (24, 33) and in cholangiocytes (15, 27), suggest that analogous mechanisms of glucose-driven water absorption are operative in both the kidney and liver. The high value of Pf we observed, as well as the inhibition of biliary water absorption by HgCl2, provides further evidence that glucose-driven movement of water in cholangiocytes is AQP mediated. This conclusion is consistent with our previous observations that cholangiocytes express a number of AQPs, which are presumably responsible for the large amount of water transported by the biliary epithelia (6, 21), and with recent studies demonstrating that the osmotic water permeability of perfused proximal kidney tubules, which actively absorb D-glucose by SGLT1, was reduced in AQP1-knockout mice by 80% (28). Indeed, net fluid absorption by this segment of the nephron determined in both perfused tubules and in vivo micropuncture studies was reduced in AQP1-knockout mice by 50% (30). The importance of AQP1 in water movement across cell membranes in response to transported glucose was also demonstrated in experiments employing expression of AQP1 and SGLT1 in Xenopus oocytes (31). The results suggested that, although SGLT1 has several different roles in water transport (9, 17, 22), it is principally involved in generating an osmotic driving force for aquaporins; this observation is in complete agreement with our findings and interpretations.
Our complementary in vivo studies showed that perturbations affecting the absorption of glucose from bile by cholangiocytes also affect ductal bile secretion. Infusion of D-glucose into the portal vein resulted in an increase of D-glucose absorption from bile by intrahepatic bile ducts and a decrease in bile flow. When absorption of glucose from bile was inhibited by phlorizin, the concentrations of biliary glucose increased, as did bile secretion. These results are consistent with previous observations that bile flow diminished progressively in rats as the concentration of glucose in plasma increased after infusion of D-glucose into the femoral vein (12) and that the rate of bile secretion decreased by about one-fifth when isolated rat livers were perfused with solutions containing 15 mM D-glucose (16). Our data are also consistent with the previous observation that phlorizin caused a marked increase in bile glucose concentration when infused into the portal vein, although plasma levels did not change significantly (12). However, contrary to findings in earlier studies that phlorizin had no effect on bile flow in rats (12), we found that bile flow increased in phlorizin-treated rats by 11.7%. The changes in total bile flow after phlorizin were moderate but quantitatively important because, in the rat, intrahepatic bile ducts contribute a relatively small amount to total bile secretion. Studies employing the segmented retrograde intrabiliary injection technique in rats also demonstrated that phlorizin inhibited absorption of biliary glucose and moderately increased bile flow (25). Thus the changes in total bile flow that we observed in our in vivo experiments may reflect a physiological response of intrahepatic bile ducts to changes in biliary glucose.
Our results and our interpretation of them may have pathophysiological relevance. Decreased bile flow in diabetic rats (5, 11, 18), in rats maintained on parenteral glucose (26), and in patients receiving total parenteral alimentation (1) has been reported; these data suggest that absorption of large amounts of D-glucose from bile by cholangiocytes may lead to increased water absorption and thus contribute to the cholestasis seen in these conditions (1, 11, 26).
In summary, we have directly demonstrated that D-glucose
absorbed from the lumen of intrahepatic bile ducts drives water
absorption by biliary epithelia and have proposed a model describing
these observations (Fig. 7). From both in
vitro microperfusion studies and in vivo studies, we conclude that
glucose transport by cholangiocytes is intimately involved with
cholangiocyte water movement and, hence, ductal bile formation.
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ACKNOWLEDGEMENTS |
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We thank Deb Hintz for secretarial assistance.
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FOOTNOTES |
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This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-24031 (N. F. LaRusso) and by the Mayo Foundation.
Address for reprint requests and other correspondence: N. F. LaRusso, Center for Basic Research in Digestive Diseases, Mayo Clinic, 200 First St., SW, Rochester, MN 55905 (E-mail: larusso.nicholas{at}mayo.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
May 15, 2002;10.1152/ajpcell.00118.2002
Received 14 March 2002; accepted in final form 1 May 2002.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Balistreri, WF,
and
Bove KE.
Hepatobiliary consequences of parenteral alimentation.
In: Progress in Liver Diseases, edited by Popper H,
and Schaffner F.. Philadelphia: Saunders, 1990, p. 567-601.
2.
Bank, N,
and
Aynedjian H.
Progressive increases in luminal glucose stimulate proximal sodium absorption in normal and diabetic rats.
J Clin Invest
86:
309-316,
1990[ISI][Medline].
3.
Barfuss, DW,
and
Schafer JA.
Differences in active and passive glucose transport along the proximal nephron.
Am J Physiol Renal Fluid Electrolyte Physiol
240:
F322-F332,
1981.
4.
Barrett, KE,
and
Dharmsathaphorn K.
Transport of water and electrolytes in the gastrointestinal tract: physiological mechanisms, regulation, and methods of study.
In: Clinical Disorders of Fluid and Electrolyte Metabolism (5th ed.), edited by Narins RG.. New York: McGraw-Hill, 1994, p. 493-519.
5.
Carnovale, CE,
Marinelli RA,
and
Rodriguez-Caray E.
A bile flow decrease and altered bile composition in streptozotocin-treated rats.
Biochem Pharmacol
35:
2625-2628,
1986[ISI][Medline].
6.
Cova, E,
Gong AY,
Marinelli RA,
and
LaRusso NF.
Water movement across rat bile duct units is transcellular and channel-mediated.
Hepatology
34:
456-463,
2001[ISI][Medline].
7.
Deen, PMT,
Nielsen S,
Bindels RJM,
and
van Os CH.
Apical and basolateral expression of aquaporin-1 in transfected MDCK and LLC-PK cells and functional evaluation of their transcellular osmotic water permeabilities.
Pflügers Arch
433:
780-787,
1997[ISI][Medline].
8.
Deetjen, P,
and
Boylan JW.
Glucose reabsorption in the rat kidney. Microperfusion studies.
Pflügers Arch
299:
19-29,
1968[ISI].
9.
Duquette, PP,
Bissonnette P,
and
Lapointe JY.
Local osmotic gradients drive the water flux associated with Na+/glucose cotransport.
Proc Natl Acad Sci USA
98:
3796-3801,
2001
10.
Fordtran, JS.
Stimulation of active and passive sodium absorption by sugars in the human jejunum.
J Clin Invest
55:
728-737,
1975[ISI][Medline].
11.
Garcia-Marin, JJ,
Villanueva GR,
and
Esteller A.
Diabetes-induced cholestasis in the rat: possible role of hyperglycemia and hypoinsulinemia.
Hepatology
8:
332-340,
1988[ISI][Medline].
12.
Guzelian, P,
and
Boyer JL.
Glucose reabsorption from bile. Evidence for a biliohepatic circulation.
J Clin Invest
53:
526-535,
1974[ISI][Medline].
13.
Knight, TF,
Senekjian HO,
Sansom S,
and
Weinman EJ.
Effects of intraluminal D-glucose and probenecid on urate absorption in the rat proximal tubule.
Am J Physiol Renal Fluid Electrolyte Physiol
236:
F526-F529,
1979
14.
Kuwahara, M,
Shi LB,
Marumo F,
and
Verkman AS.
Transcellular water flow modulates water channel exocytosis and endocytosis in kidney collecting tubule.
J Clin Invest
88:
423-429,
1991[ISI][Medline].
15.
Lazaridis, KN,
Pham L,
Vroman B,
De Groen PC,
and
LaRusso NF.
Kinetic and molecular identification of sodium-dependent glucose transporter in normal rat cholangiocytes.
Am J Physiol Gastrointest Liver Physiol
272:
G1168-G1174,
1997
16.
Lira, M,
Schteingart CD,
Steinbach JH,
Lambert K,
McRoberts JA,
and
Hofmann AF.
Sugar absorption by the biliary ductular epithelium of the rat: evidence for two transport systems.
Gastroenterology
102:
563-571,
1992[ISI][Medline].
17.
Loo, DDF,
Hirayama BA,
Meinild AK,
Chandy G,
Zeuthen T,
and
Wright EM.
Passive water and ion transport by cotransporters.
J Physiol
518:
195-202,
1999
18.
Marin, JJG,
Herreros M,
Villanueva GR,
Perez-Barriocanal F,
El-Mir MY,
and
Medina JM.
Effect of streptozotocin-induced diabetes on sex differences in biliary lipid secretion in the rat.
Biochim Biophys Acta
1043:
106-112,
1990[ISI][Medline].
19.
Masyuk, AI,
Gong AY,
Kip S,
Burke MJ,
and
LaRusso NF.
Perfused rat intrahepatic bile ducts secrete and absorb water, solute, and ions.
Gastroenterology
119:
1672-1680,
2000[ISI][Medline].
20.
Masyuk, TV,
Ritman EL,
and
LaRusso NF.
Heterogeneity of bile flow along the intrahepatic biliary tree (Abstract).
Hepatology
34:
522A,
2001.
21.
Masyuk, AI,
Marinelli RA,
and
LaRusso NF.
Water transport by epithelia of the digestive tract.
Gastroenterology
122:
545-562,
2002[ISI][Medline].
22.
Meinild, AK,
Klaerke DA,
Loo DDF,
Wright EM,
and
Zeuthen T.
The human Na+-glucose cotransporter is a molecular water pump.
J Physiol
508:
15-21,
1998
23.
Montrose, MH,
Keely SJ,
and
Barrett KE.
Electrolyte secretion and absorption: small intestine and colon.
In: Textbook of Gastroenterology (3rd ed.), edited by Yamada T.. Philadelphia: Lippincott Williams and Wilkins, 1999, vol. 1, p. 320-355.
24.
Nielsen, S,
Frokiaer J,
Marples D,
Kwon TH,
Agre P,
and
Knepper MA.
Aquaporins in the kidney: from molecules to medicine.
Physiol Rev
82:
205-244,
2002
25.
Olson, JR,
and
Fujimoto JM.
Demonstration of a D-glucose transport system in the biliary tree of the rat by use of the segmented retrograde intrabiliary injection technique.
Biochem Pharmacol
29:
213-219,
1980[ISI][Medline].
26.
Rivera, A,
Bhatia J,
Rassin DK,
Gourley WK,
and
Catarau E.
In vivo biliary function in the adult rat: the effect of parenteral glucose and amino acids.
J Parenter Enteral Nutr
13:
240-245,
1989[Abstract].
27.
Roberts, SK,
Yano M,
Ueno Y,
Pham L,
Alpini G,
Agre P,
and
LaRusso NF.
Cholangiocytes express the aquaporin CHIP and transport water via a channel-mediated mechanism.
Proc Natl Acad Sci USA
91:
13009-13013,
1994
28.
Schnermann, J,
Chou CL,
Ma T,
Traynor T,
Knepper MA,
and
Verkman AS.
Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice.
Proc Natl Acad Sci USA
95:
9660-9664,
1998
29.
Tune, BM,
and
Burg MB.
Glucose transport by proximal renal tubules.
Am J Physiol
221:
580-585,
1971
30.
Vallon, V,
Verkman AS,
and
Schnermann J.
Luminal hypotonicity in proximal tubules of aquaporin-1-knockout mice.
Am J Physiol Renal Physiol
278:
F1030-F1033,
2000
31.
Zeuthen, T,
Meinild AK,
Loo DDF,
Wright EM,
and
Klaerke DA.
Isotonic transport by the Na+-glucose cotransporter SGLT1 from humans and rabbit.
J Physiol
531.3:
631-644,
2001
32.
Weinman, EJ,
Suki WN,
and
Eknoyan G.
D-Glucose enhancement of water reabsorption in proximal tubule of the rat kidney.
Am J Physiol
231:
777-780,
1976
33.
Wright, EM.
Renal Na+-glucose cotransporters.
Am J Physiol Renal Physiol
280:
F10-F18,
2001