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Does apical membrane GLUT2 have a role in intestinal glucose uptake?

Naftalin RJ - F1000Res (2014)

Bottom Line: Since the other apical membrane sugar transporter, GLUT5, is insensitive to inhibition by either cytochalasin B, or phloretin, GLUT2 was deduced to be the low affinity sugar transport route.As in its uninhibited state, polarized intestinal glucose absorption depends both on coupled entry of glucose and sodium across the brush border membrane and on the enterocyte cytosolic glucose concentration exceeding that in both luminal and submucosal interstitial fluids, upregulation of GLUT2 within the intestinal brush border will usually stimulate downhill glucose reflux to the intestinal lumen from the enterocytes; thereby reducing, rather than enhancing net glucose absorption across the luminal surface.These states are simulated with a computer model generating solutions to the differential equations for glucose, Na and water flows between luminal, cell, interstitial and capillary compartments.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and BHF Centre of Research Excellence, King's College London, School of Medicine, London, SE1 9HN, UK.

ABSTRACT
It has been proposed that the non-saturable component of intestinal glucose absorption, apparent following prolonged exposure to high intraluminal glucose concentrations, is mediated via the low affinity glucose and fructose transporter, GLUT2, upregulated within the small intestinal apical border. The evidence that the non-saturable transport component is mediated via an apical membrane sugar transporter is that it is inhibited by phloretin, after exposure to phloridzin. Since the other apical membrane sugar transporter, GLUT5, is insensitive to inhibition by either cytochalasin B, or phloretin, GLUT2 was deduced to be the low affinity sugar transport route. As in its uninhibited state, polarized intestinal glucose absorption depends both on coupled entry of glucose and sodium across the brush border membrane and on the enterocyte cytosolic glucose concentration exceeding that in both luminal and submucosal interstitial fluids, upregulation of GLUT2 within the intestinal brush border will usually stimulate downhill glucose reflux to the intestinal lumen from the enterocytes; thereby reducing, rather than enhancing net glucose absorption across the luminal surface. These states are simulated with a computer model generating solutions to the differential equations for glucose, Na and water flows between luminal, cell, interstitial and capillary compartments. The model demonstrates that uphill glucose transport via SGLT1 into enterocytes, when short-circuited by any passive glucose carrier in the apical membrane, such as GLUT2, will reduce transcellular glucose absorption and thereby lead to increased paracellular flow. The model also illustrates that apical GLUT2 may usefully act as an osmoregulator to prevent excessive enterocyte volume change with altered luminal glucose concentrations.

No MeSH data available.


Related in: MedlinePlus

Simulation of altered apical membrane GLUT2 activity on intestinal glucose fluxes from zero (PanelA) to an arbitrary of maximal flux value of 2 (PanelB).The simulations show the glucose fluxes via apical SGLT1 (blue); apical GLUT2 (red); paracellular pathway (green); the total transluminal membrane, (SGLT1 + GLUT2 + paracellular fluxes), (black) and interstitial to capillary flow (pink crosses) inset on the black square. The main effect of increasing GLUT2 is to cause a negative glucose flux (backflux) via GLUT2 (PanelB). This is accompanied by a increased paracellular flux without any significant change in net transluminal or transepithelial glucose flux. The point at which paracellular glucose flux and SGLT1 flux are equal lies between 20 and 30 mM as has been previously observed4–6. This value is used as one of the key registration points for the model.The cytosolic (red) interstitial (blue) and mean capillary glucose concentrations (black) and enterocyte volume per unit weight of tissue (green) are shown in panelC with zero apical GLUT2 and in PanelD with GLUT2 Vmax = 2.Increased apical GLUT2 activity decreases cytosolic glucose concentration (panelD). With rising luminal glucose concentration raised GLUT2 activity prevents the non-linear increase in enterocyte volume seen with zero GLUT2 (PanelC).
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f2: Simulation of altered apical membrane GLUT2 activity on intestinal glucose fluxes from zero (PanelA) to an arbitrary of maximal flux value of 2 (PanelB).The simulations show the glucose fluxes via apical SGLT1 (blue); apical GLUT2 (red); paracellular pathway (green); the total transluminal membrane, (SGLT1 + GLUT2 + paracellular fluxes), (black) and interstitial to capillary flow (pink crosses) inset on the black square. The main effect of increasing GLUT2 is to cause a negative glucose flux (backflux) via GLUT2 (PanelB). This is accompanied by a increased paracellular flux without any significant change in net transluminal or transepithelial glucose flux. The point at which paracellular glucose flux and SGLT1 flux are equal lies between 20 and 30 mM as has been previously observed4–6. This value is used as one of the key registration points for the model.The cytosolic (red) interstitial (blue) and mean capillary glucose concentrations (black) and enterocyte volume per unit weight of tissue (green) are shown in panelC with zero apical GLUT2 and in PanelD with GLUT2 Vmax = 2.Increased apical GLUT2 activity decreases cytosolic glucose concentration (panelD). With rising luminal glucose concentration raised GLUT2 activity prevents the non-linear increase in enterocyte volume seen with zero GLUT2 (PanelC).

Mentions: However, even with high rates of vascular perfusion, the interstitial glucose concentration approximates to that of the luminal concentration. Consequently, as luminal glucose concentrations are raised, even although interstitial capillary glucose clearance is increased, the enterocyte cytosolic concentrations continuously rises, (Figure 2C and 2D)11.


Does apical membrane GLUT2 have a role in intestinal glucose uptake?

Naftalin RJ - F1000Res (2014)

Simulation of altered apical membrane GLUT2 activity on intestinal glucose fluxes from zero (PanelA) to an arbitrary of maximal flux value of 2 (PanelB).The simulations show the glucose fluxes via apical SGLT1 (blue); apical GLUT2 (red); paracellular pathway (green); the total transluminal membrane, (SGLT1 + GLUT2 + paracellular fluxes), (black) and interstitial to capillary flow (pink crosses) inset on the black square. The main effect of increasing GLUT2 is to cause a negative glucose flux (backflux) via GLUT2 (PanelB). This is accompanied by a increased paracellular flux without any significant change in net transluminal or transepithelial glucose flux. The point at which paracellular glucose flux and SGLT1 flux are equal lies between 20 and 30 mM as has been previously observed4–6. This value is used as one of the key registration points for the model.The cytosolic (red) interstitial (blue) and mean capillary glucose concentrations (black) and enterocyte volume per unit weight of tissue (green) are shown in panelC with zero apical GLUT2 and in PanelD with GLUT2 Vmax = 2.Increased apical GLUT2 activity decreases cytosolic glucose concentration (panelD). With rising luminal glucose concentration raised GLUT2 activity prevents the non-linear increase in enterocyte volume seen with zero GLUT2 (PanelC).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4309173&req=5

f2: Simulation of altered apical membrane GLUT2 activity on intestinal glucose fluxes from zero (PanelA) to an arbitrary of maximal flux value of 2 (PanelB).The simulations show the glucose fluxes via apical SGLT1 (blue); apical GLUT2 (red); paracellular pathway (green); the total transluminal membrane, (SGLT1 + GLUT2 + paracellular fluxes), (black) and interstitial to capillary flow (pink crosses) inset on the black square. The main effect of increasing GLUT2 is to cause a negative glucose flux (backflux) via GLUT2 (PanelB). This is accompanied by a increased paracellular flux without any significant change in net transluminal or transepithelial glucose flux. The point at which paracellular glucose flux and SGLT1 flux are equal lies between 20 and 30 mM as has been previously observed4–6. This value is used as one of the key registration points for the model.The cytosolic (red) interstitial (blue) and mean capillary glucose concentrations (black) and enterocyte volume per unit weight of tissue (green) are shown in panelC with zero apical GLUT2 and in PanelD with GLUT2 Vmax = 2.Increased apical GLUT2 activity decreases cytosolic glucose concentration (panelD). With rising luminal glucose concentration raised GLUT2 activity prevents the non-linear increase in enterocyte volume seen with zero GLUT2 (PanelC).
Mentions: However, even with high rates of vascular perfusion, the interstitial glucose concentration approximates to that of the luminal concentration. Consequently, as luminal glucose concentrations are raised, even although interstitial capillary glucose clearance is increased, the enterocyte cytosolic concentrations continuously rises, (Figure 2C and 2D)11.

Bottom Line: Since the other apical membrane sugar transporter, GLUT5, is insensitive to inhibition by either cytochalasin B, or phloretin, GLUT2 was deduced to be the low affinity sugar transport route.As in its uninhibited state, polarized intestinal glucose absorption depends both on coupled entry of glucose and sodium across the brush border membrane and on the enterocyte cytosolic glucose concentration exceeding that in both luminal and submucosal interstitial fluids, upregulation of GLUT2 within the intestinal brush border will usually stimulate downhill glucose reflux to the intestinal lumen from the enterocytes; thereby reducing, rather than enhancing net glucose absorption across the luminal surface.These states are simulated with a computer model generating solutions to the differential equations for glucose, Na and water flows between luminal, cell, interstitial and capillary compartments.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and BHF Centre of Research Excellence, King's College London, School of Medicine, London, SE1 9HN, UK.

ABSTRACT
It has been proposed that the non-saturable component of intestinal glucose absorption, apparent following prolonged exposure to high intraluminal glucose concentrations, is mediated via the low affinity glucose and fructose transporter, GLUT2, upregulated within the small intestinal apical border. The evidence that the non-saturable transport component is mediated via an apical membrane sugar transporter is that it is inhibited by phloretin, after exposure to phloridzin. Since the other apical membrane sugar transporter, GLUT5, is insensitive to inhibition by either cytochalasin B, or phloretin, GLUT2 was deduced to be the low affinity sugar transport route. As in its uninhibited state, polarized intestinal glucose absorption depends both on coupled entry of glucose and sodium across the brush border membrane and on the enterocyte cytosolic glucose concentration exceeding that in both luminal and submucosal interstitial fluids, upregulation of GLUT2 within the intestinal brush border will usually stimulate downhill glucose reflux to the intestinal lumen from the enterocytes; thereby reducing, rather than enhancing net glucose absorption across the luminal surface. These states are simulated with a computer model generating solutions to the differential equations for glucose, Na and water flows between luminal, cell, interstitial and capillary compartments. The model demonstrates that uphill glucose transport via SGLT1 into enterocytes, when short-circuited by any passive glucose carrier in the apical membrane, such as GLUT2, will reduce transcellular glucose absorption and thereby lead to increased paracellular flow. The model also illustrates that apical GLUT2 may usefully act as an osmoregulator to prevent excessive enterocyte volume change with altered luminal glucose concentrations.

No MeSH data available.


Related in: MedlinePlus