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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 effects of varying paracellular glucose permeability on intestinal glucose fluxes and accumulation.The effects of varying paracellular glucose permeability Pglc from 0 to 0.02 cm s-1 are shown inFigure 3A increasing Pglc on paracellular glucose flux (Blue) .As Pglc is increased from zero the point of equality of paracellular glucose flux Jglpc with glucose flux via SGLT1 decreases from infinity at Pglc = 0 to around 20–30 mM luminal glucose when Pglc = 0.01–0.02 cm s-1.Increases Pglc raises interstitial glucose concentrations 3C (blue) and in parallel, cysosolic concentrationsFigure 3C (red). The reduction in glucose gradient across the basolateral membrane with raised Pglc reduces and then reverses glucose flux via GLUT2 (Figure 3B).
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f3: Simulation of effects of varying paracellular glucose permeability on intestinal glucose fluxes and accumulation.The effects of varying paracellular glucose permeability Pglc from 0 to 0.02 cm s-1 are shown inFigure 3A increasing Pglc on paracellular glucose flux (Blue) .As Pglc is increased from zero the point of equality of paracellular glucose flux Jglpc with glucose flux via SGLT1 decreases from infinity at Pglc = 0 to around 20–30 mM luminal glucose when Pglc = 0.01–0.02 cm s-1.Increases Pglc raises interstitial glucose concentrations 3C (blue) and in parallel, cysosolic concentrationsFigure 3C (red). The reduction in glucose gradient across the basolateral membrane with raised Pglc reduces and then reverses glucose flux via GLUT2 (Figure 3B).

Mentions: Uphill glucose transport via the apical membrane sodium-glucose cotransporter SGLT1 generates polarized sugar flow, causing the intracellular glucose concentration to increase: eventually the cytosolic and also interstitial glucose concentrations may exceed the luminal concentration35. Once these conditions are met, glucose will reflux back into the intestinal lumen via passive transporters in the apical membrane, or via the tight junction (Figure 1A). If the Vmax of the passive apical membrane glucose transporters is raised, then owing to enhanced glucose reflux via GLUT2, net glucose influx across the apical membrane will be reduced. However, net glucose uptake across the luminal surface, including the paracellular pathways may be augmented. This increase in paracellular glucose flow arises from decreased transcellular flow. The resulting slight decrease in interstitial fluid glucose concentration increases the gradient between the intestinal lumen and interstitial fluid, (Figure 1B) andFigure 3(A–C).


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

Naftalin RJ - F1000Res (2014)

Simulation of effects of varying paracellular glucose permeability on intestinal glucose fluxes and accumulation.The effects of varying paracellular glucose permeability Pglc from 0 to 0.02 cm s-1 are shown inFigure 3A increasing Pglc on paracellular glucose flux (Blue) .As Pglc is increased from zero the point of equality of paracellular glucose flux Jglpc with glucose flux via SGLT1 decreases from infinity at Pglc = 0 to around 20–30 mM luminal glucose when Pglc = 0.01–0.02 cm s-1.Increases Pglc raises interstitial glucose concentrations 3C (blue) and in parallel, cysosolic concentrationsFigure 3C (red). The reduction in glucose gradient across the basolateral membrane with raised Pglc reduces and then reverses glucose flux via GLUT2 (Figure 3B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Simulation of effects of varying paracellular glucose permeability on intestinal glucose fluxes and accumulation.The effects of varying paracellular glucose permeability Pglc from 0 to 0.02 cm s-1 are shown inFigure 3A increasing Pglc on paracellular glucose flux (Blue) .As Pglc is increased from zero the point of equality of paracellular glucose flux Jglpc with glucose flux via SGLT1 decreases from infinity at Pglc = 0 to around 20–30 mM luminal glucose when Pglc = 0.01–0.02 cm s-1.Increases Pglc raises interstitial glucose concentrations 3C (blue) and in parallel, cysosolic concentrationsFigure 3C (red). The reduction in glucose gradient across the basolateral membrane with raised Pglc reduces and then reverses glucose flux via GLUT2 (Figure 3B).
Mentions: Uphill glucose transport via the apical membrane sodium-glucose cotransporter SGLT1 generates polarized sugar flow, causing the intracellular glucose concentration to increase: eventually the cytosolic and also interstitial glucose concentrations may exceed the luminal concentration35. Once these conditions are met, glucose will reflux back into the intestinal lumen via passive transporters in the apical membrane, or via the tight junction (Figure 1A). If the Vmax of the passive apical membrane glucose transporters is raised, then owing to enhanced glucose reflux via GLUT2, net glucose influx across the apical membrane will be reduced. However, net glucose uptake across the luminal surface, including the paracellular pathways may be augmented. This increase in paracellular glucose flow arises from decreased transcellular flow. The resulting slight decrease in interstitial fluid glucose concentration increases the gradient between the intestinal lumen and interstitial fluid, (Figure 1B) andFigure 3(A–C).

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