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. 2008 May 15;94(10):3912-23.
doi: 10.1529/biophysj.107.122531. Epub 2008 Jan 30.

Osmotic water transport with glucose in GLUT2 and SGLT

Richard J Naftalin  1
Affiliations

Osmotic water transport with glucose in GLUT2 and SGLT

Richard J Naftalin. Biophys J. .

Abstract

Carrier-mediated water cotransport is currently a favored explanation for water movement against an osmotic gradient. The vestibule within the central pore of Na(+)-dependent cotransporters or GLUT2 provides the necessary precondition for an osmotic mechanism, explaining this phenomenon without carriers. Simulating equilibrative glucose inflow via the narrow external orifice of GLUT2 raises vestibular tonicity relative to the external solution. Vestibular hypertonicity causes osmotic water inflow, which raises vestibular hydrostatic pressure and forces water, salt, and glucose into the outer cytosolic layer via its wide endofacial exit. Glucose uptake via GLUT2 also raises oocyte tonicity. Glucose exit from preloaded cells depletes the vestibule of glucose, making it hypotonic and thereby inducing water efflux. Inhibiting glucose exit with phloretin reestablishes vestibular hypertonicity, as it reequilibrates with the cytosolic glucose and net water inflow recommences. Simulated Na(+)-glucose cotransport demonstrates that active glucose accumulation within the vestibule generates water flows simultaneously with the onset of glucose flow and before any flow external to the transporter caused by hypertonicity in the outer cytosolic layers. The molar ratio of water/glucose flow is seen now to relate to the ratio of hydraulic and glucose permeability rather than to water storage capacity of putative water carriers.

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Figures

FIGURE 1
FIGURE 1
Diagram showing routes of water flow across GLUT2 or SGLT and the oocyte membrane. Two routes are shown. One is via the transporter through which water and cotransported solutes pass via the external tight opening, then the vestibule, then via the wide vestibular exit into the external cytosolic layer. The other route permits only water flow determined by the osmotic pressure difference between the outer cytosol and the external solution.
FIGURE 2
FIGURE 2
Simulation of effects of 3-OMG flows (20 mM) on water flows in oocytes expressing GLUT2. (A) The simulated oocyte percentage volume change (solid line) is superimposed on the observed data (open circles) obtained by Zeuthen et al. (7). The dashed line shows the simulated average cytosolic glucose concentration mM. The leftmost vertical dotted line indicates the time of isotonic addition of 3-OMG (20 mM). The second vertical line is when 3-OMG is removed and the third vertical line is when phloretin is added. (B) The simulated changes in glucose concentration are illustrated as follows in the external solution (solid line), vestibule (dash-dotted), outer cytosolic layer (long dashed), and averaged inner cytosolic layers (short dashed). (C) The simulated changes in osmolarity of the impermeant solute (KCl) are shown in D, and the rates of fluid inflow via the transporter (long dashed) and via the membrane (short dashed) and the total flow (solid line) are shown. (E) The concentrations of glucose mM in the vestibule and from the most external cytosolic layer, 3, to innermost layer, 10, are shown. (F) The total osmolarity (glucose mM + impermeant solute mOsm) in the vestibule (solid line), outer cytosolic layer, (dash-dotted), and average cytosol (dashed) is shown. (C and D) Outputs from some layers are omitted for clarity.
FIGURE 3
FIGURE 3
Simulation of effects of 1 mM 3-O methyl D-glucose (3-OMG) and 20 mM urea and phloridzin on water flows into oocytes expressing SGLT1. (A) The simulated oocyte percentage volume change (solid line) superimposed on the observed experimental data obtained from Zeuthen et al. (23) (open circles). The first period starts upon exposure to isotonic 1 mM 3-OMG, the second upon addition of 20 mM hypertonic urea + 1 mM 3-OMG, the third upon removal of urea, the fourth upon isotonic removal of 3-OMG and addition of phloridzin (negligible tonicity), and the fifth period upon addition of 20 mM hypertonic urea + phloridzin. (B) The changes in compartmental 3-OMG during the five experimental periods shown in A. (C) The compartmental and extracellular changes in total osmolarity. (D) The separate water flow rates via the transporter, the membrane, and the total transmembrane flows. (E) The changes in vestibular and unstirred layer total osmolarity mOsm, superimposed on the water flow rates via the transporter and membrane using a 100× faster time base than in A and D.
FIGURE 4
FIGURE 4
Simulation of the changes in the molar ratio of water/3-OMG inflow via Glut2. The lines shown indicate the effects of changing the parameter values of the transporter Pw12 on inflow phase 1 and outflow phase 2 with varying values of the hydraulic permeability.
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References

    1. Curran, P. F., and J. R. MacIntosh. 1962. A model system for biological water transport. Nature. 193:347–348. - PubMed
    1. Zeuthen, T., and W. D. Stein. 1994. Cotransport of salt and water in membrane proteins: membrane proteins as osmotic engines. J. Membr. Biol. 137:179–195. - PubMed
    1. Charron, F. M., M. G. Blanchard, and J. Y. Lapointe. 2006. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport. Biophys. J. 90:3546–3554. - PMC - PubMed
    1. Duquette, P. P., P. Bissonnette, and J. Y. Lapointe. 2001. Local osmotic gradients drive the water flux associated with Na(+)/glucose cotransport. Proc. Natl. Acad. Sci. USA. 98:3796–3801. - PMC - PubMed
    1. Lapointe, J. Y. 2007. Response to Zeuthen and Zeuthen's comment to the editor: enough local hypertonicity is enough. Biophys. J. 93:1417–1419.

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