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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 sequential additions of phloridzin then phloretin to the luminal fluid on intestinal glucose fluxes.GLUT2 is present in the apical membrane Vmax 2 and the capillary perfusion rate = 10 is similar to that shown inFigure 2 panelsB andD. The luminal glucose is 30 mM and afferent capillary glucose is 5 mM to simulate the conditions used by Kellett & Helliwell 20001. InFigure 4, panelsA andB inhibition of SGLT1 activity at 0.5h to zero reduces glucose flux via SGLT1 to zero. Simultaneously glucose flux via GLUT2 increases thereby reversing the backflux from -1.1. to 0.05 and also paracellular glucose flux increases from 0.55 to 0.95. In panelsC andD the glucose concentration changes in the cytosol (red) interstitial fluid (blue) capillary fluid (black) and cytosolic volume (green). Following phloridzin addition and inhibition of SGLT1, cytosolic glucose falls from 33 to 30 mM; cytosolic volume falls from 0.62 to 0.56 ml at 1 hour without significant changes in capillary or interstitial fluid glucose concentration. This explains both the fall in glucose reflux via GLUT2 and the decrease in basolateral membrane flux is compensated by the rise in paracellular flux thereby ifying interstitial glucose concentration changes.Phloretin addition at 1h is simulated by blocking apical GLUT2 (panelA) and by blocking both apical GLUT2 and paracellular glucose and Na permeability (panelB). GLUT2 fluxes fall to zero in both panelsA andB and in panelA there is a small increase in paracellular glucose flow but the total transluminal glucose flux is unaffected by addition of phloretin after phloridzin. There is a small decrease in cytosolic volume from 0.56 to ≈ 0.55. the paracellular flux falls to zero as does the transluminal glucose flux in panelB, simulating the effect observed by Kellett and Helliwell 20001. This is accompanied by a large decrease in cell volume from 0.56 to 0.51 ml. Since no net glucose transport now occurs from the luminal fluid, capillary glucose concentration also decreases to 5 mM.
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f4: Simulation of sequential additions of phloridzin then phloretin to the luminal fluid on intestinal glucose fluxes.GLUT2 is present in the apical membrane Vmax 2 and the capillary perfusion rate = 10 is similar to that shown inFigure 2 panelsB andD. The luminal glucose is 30 mM and afferent capillary glucose is 5 mM to simulate the conditions used by Kellett & Helliwell 20001. InFigure 4, panelsA andB inhibition of SGLT1 activity at 0.5h to zero reduces glucose flux via SGLT1 to zero. Simultaneously glucose flux via GLUT2 increases thereby reversing the backflux from -1.1. to 0.05 and also paracellular glucose flux increases from 0.55 to 0.95. In panelsC andD the glucose concentration changes in the cytosol (red) interstitial fluid (blue) capillary fluid (black) and cytosolic volume (green). Following phloridzin addition and inhibition of SGLT1, cytosolic glucose falls from 33 to 30 mM; cytosolic volume falls from 0.62 to 0.56 ml at 1 hour without significant changes in capillary or interstitial fluid glucose concentration. This explains both the fall in glucose reflux via GLUT2 and the decrease in basolateral membrane flux is compensated by the rise in paracellular flux thereby ifying interstitial glucose concentration changes.Phloretin addition at 1h is simulated by blocking apical GLUT2 (panelA) and by blocking both apical GLUT2 and paracellular glucose and Na permeability (panelB). GLUT2 fluxes fall to zero in both panelsA andB and in panelA there is a small increase in paracellular glucose flow but the total transluminal glucose flux is unaffected by addition of phloretin after phloridzin. There is a small decrease in cytosolic volume from 0.56 to ≈ 0.55. the paracellular flux falls to zero as does the transluminal glucose flux in panelB, simulating the effect observed by Kellett and Helliwell 20001. This is accompanied by a large decrease in cell volume from 0.56 to 0.51 ml. Since no net glucose transport now occurs from the luminal fluid, capillary glucose concentration also decreases to 5 mM.

Mentions: Simulation of the temporal effects of phloridzin on intestinal glucose uptake exposed to luminal glucose 30 mM1 shows that whilst inhibiting glucose influx via SGLT1, net glucose efflux via GLUT2 is abolished as a result of the decreased uphill glucose accumulation in the cytosol. Hence glucose flux across the basolateral membrane is reduced; however, because the interstitial glucose decreases due to diminished, transcellular flow paracellular glucose influx rises. Consequently, the net effect of SGLT1 inhibition by phloridzin on net glucose absorption is negligible, as observed in rabbit ileum pre-incubated with glucose9. Following phloridzin inhibition of SGLT1, cytosolic glucose falls from ≈ 32 mM to ≈ 17 mM as simulated here (Figure 4A and 4B).


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

Naftalin RJ - F1000Res (2014)

Simulation of sequential additions of phloridzin then phloretin to the luminal fluid on intestinal glucose fluxes.GLUT2 is present in the apical membrane Vmax 2 and the capillary perfusion rate = 10 is similar to that shown inFigure 2 panelsB andD. The luminal glucose is 30 mM and afferent capillary glucose is 5 mM to simulate the conditions used by Kellett & Helliwell 20001. InFigure 4, panelsA andB inhibition of SGLT1 activity at 0.5h to zero reduces glucose flux via SGLT1 to zero. Simultaneously glucose flux via GLUT2 increases thereby reversing the backflux from -1.1. to 0.05 and also paracellular glucose flux increases from 0.55 to 0.95. In panelsC andD the glucose concentration changes in the cytosol (red) interstitial fluid (blue) capillary fluid (black) and cytosolic volume (green). Following phloridzin addition and inhibition of SGLT1, cytosolic glucose falls from 33 to 30 mM; cytosolic volume falls from 0.62 to 0.56 ml at 1 hour without significant changes in capillary or interstitial fluid glucose concentration. This explains both the fall in glucose reflux via GLUT2 and the decrease in basolateral membrane flux is compensated by the rise in paracellular flux thereby ifying interstitial glucose concentration changes.Phloretin addition at 1h is simulated by blocking apical GLUT2 (panelA) and by blocking both apical GLUT2 and paracellular glucose and Na permeability (panelB). GLUT2 fluxes fall to zero in both panelsA andB and in panelA there is a small increase in paracellular glucose flow but the total transluminal glucose flux is unaffected by addition of phloretin after phloridzin. There is a small decrease in cytosolic volume from 0.56 to ≈ 0.55. the paracellular flux falls to zero as does the transluminal glucose flux in panelB, simulating the effect observed by Kellett and Helliwell 20001. This is accompanied by a large decrease in cell volume from 0.56 to 0.51 ml. Since no net glucose transport now occurs from the luminal fluid, capillary glucose concentration also decreases to 5 mM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Simulation of sequential additions of phloridzin then phloretin to the luminal fluid on intestinal glucose fluxes.GLUT2 is present in the apical membrane Vmax 2 and the capillary perfusion rate = 10 is similar to that shown inFigure 2 panelsB andD. The luminal glucose is 30 mM and afferent capillary glucose is 5 mM to simulate the conditions used by Kellett & Helliwell 20001. InFigure 4, panelsA andB inhibition of SGLT1 activity at 0.5h to zero reduces glucose flux via SGLT1 to zero. Simultaneously glucose flux via GLUT2 increases thereby reversing the backflux from -1.1. to 0.05 and also paracellular glucose flux increases from 0.55 to 0.95. In panelsC andD the glucose concentration changes in the cytosol (red) interstitial fluid (blue) capillary fluid (black) and cytosolic volume (green). Following phloridzin addition and inhibition of SGLT1, cytosolic glucose falls from 33 to 30 mM; cytosolic volume falls from 0.62 to 0.56 ml at 1 hour without significant changes in capillary or interstitial fluid glucose concentration. This explains both the fall in glucose reflux via GLUT2 and the decrease in basolateral membrane flux is compensated by the rise in paracellular flux thereby ifying interstitial glucose concentration changes.Phloretin addition at 1h is simulated by blocking apical GLUT2 (panelA) and by blocking both apical GLUT2 and paracellular glucose and Na permeability (panelB). GLUT2 fluxes fall to zero in both panelsA andB and in panelA there is a small increase in paracellular glucose flow but the total transluminal glucose flux is unaffected by addition of phloretin after phloridzin. There is a small decrease in cytosolic volume from 0.56 to ≈ 0.55. the paracellular flux falls to zero as does the transluminal glucose flux in panelB, simulating the effect observed by Kellett and Helliwell 20001. This is accompanied by a large decrease in cell volume from 0.56 to 0.51 ml. Since no net glucose transport now occurs from the luminal fluid, capillary glucose concentration also decreases to 5 mM.
Mentions: Simulation of the temporal effects of phloridzin on intestinal glucose uptake exposed to luminal glucose 30 mM1 shows that whilst inhibiting glucose influx via SGLT1, net glucose efflux via GLUT2 is abolished as a result of the decreased uphill glucose accumulation in the cytosol. Hence glucose flux across the basolateral membrane is reduced; however, because the interstitial glucose decreases due to diminished, transcellular flow paracellular glucose influx rises. Consequently, the net effect of SGLT1 inhibition by phloridzin on net glucose absorption is negligible, as observed in rabbit ileum pre-incubated with glucose9. Following phloridzin inhibition of SGLT1, cytosolic glucose falls from ≈ 32 mM to ≈ 17 mM as simulated here (Figure 4A and 4B).

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