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Osmotic water transport with glucose in GLUT2 and SGLT.

Naftalin RJ - Biophys. J. (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: King's College London, Physiology, Waterloo Campus, London SE1 9HN, United Kingdom. richard.naftalin@kcl.ac.uk

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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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.
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fig2: 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.

Mentions: Derived parameters from GLUT2 model fitted to water inflow via GLUT2 expressed in Xenopus oocytes (7) as shown in Fig. 2


Osmotic water transport with glucose in GLUT2 and SGLT.

Naftalin RJ - Biophys. J. (2008)

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.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2367205&req=5

fig2: 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.
Mentions: Derived parameters from GLUT2 model fitted to water inflow via GLUT2 expressed in Xenopus oocytes (7) as shown in Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: King's College London, Physiology, Waterloo Campus, London SE1 9HN, United Kingdom. richard.naftalin@kcl.ac.uk

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.

Show MeSH
Related in: MedlinePlus