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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

Diagram showing the predicted effects from the simulation model of loading enterocytes with luminal fluid containing 50 mM glucose and 5 mM glucose in the capillary perfusion fluid in A normal enterocytes expressing apical membrane GLUT2 and in B GLUT2 KO enterocytes.The KO cells have higher enterocyte glucose concentrations in the proximal intestine, but higher paracellular flow and larger cell volumes. The normal enterocytes have lower cytosolic glucose concentrations and SGLT1 is more widely dispersed along the intestinal length with higher rates of glucose permeation in distal regions of the small intestine. Long term exposure may lead to higher maximal glucose absorption rates in normal intestine than with GLUT2 KO.
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f5: Diagram showing the predicted effects from the simulation model of loading enterocytes with luminal fluid containing 50 mM glucose and 5 mM glucose in the capillary perfusion fluid in A normal enterocytes expressing apical membrane GLUT2 and in B GLUT2 KO enterocytes.The KO cells have higher enterocyte glucose concentrations in the proximal intestine, but higher paracellular flow and larger cell volumes. The normal enterocytes have lower cytosolic glucose concentrations and SGLT1 is more widely dispersed along the intestinal length with higher rates of glucose permeation in distal regions of the small intestine. Long term exposure may lead to higher maximal glucose absorption rates in normal intestine than with GLUT2 KO.

Mentions: This latter effect may explain why when pigs are exposed to high carbohydrate diets raised SGLT1 protein and mRNA expression is observed in more distal intestinal regions44. More SGLT1 is also observed in duodenal epithelia of morbidly obese humans45. Increased density and increased area of intestinal SGLT1 expression implies that the intestine develops the capacity to deal with increased carbohydrate loads by absorbing more carbohydrate in aggregate, although not per unit area (Figure 5). This will generate higher concentration peaks of carbohydrate in the splanchnic circulation following absorbable carbohydrate ingestion41,45 and higher rates of splanchnic blood flow in conscious animals46–48.


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

Naftalin RJ - F1000Res (2014)

Diagram showing the predicted effects from the simulation model of loading enterocytes with luminal fluid containing 50 mM glucose and 5 mM glucose in the capillary perfusion fluid in A normal enterocytes expressing apical membrane GLUT2 and in B GLUT2 KO enterocytes.The KO cells have higher enterocyte glucose concentrations in the proximal intestine, but higher paracellular flow and larger cell volumes. The normal enterocytes have lower cytosolic glucose concentrations and SGLT1 is more widely dispersed along the intestinal length with higher rates of glucose permeation in distal regions of the small intestine. Long term exposure may lead to higher maximal glucose absorption rates in normal intestine than with GLUT2 KO.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Diagram showing the predicted effects from the simulation model of loading enterocytes with luminal fluid containing 50 mM glucose and 5 mM glucose in the capillary perfusion fluid in A normal enterocytes expressing apical membrane GLUT2 and in B GLUT2 KO enterocytes.The KO cells have higher enterocyte glucose concentrations in the proximal intestine, but higher paracellular flow and larger cell volumes. The normal enterocytes have lower cytosolic glucose concentrations and SGLT1 is more widely dispersed along the intestinal length with higher rates of glucose permeation in distal regions of the small intestine. Long term exposure may lead to higher maximal glucose absorption rates in normal intestine than with GLUT2 KO.
Mentions: This latter effect may explain why when pigs are exposed to high carbohydrate diets raised SGLT1 protein and mRNA expression is observed in more distal intestinal regions44. More SGLT1 is also observed in duodenal epithelia of morbidly obese humans45. Increased density and increased area of intestinal SGLT1 expression implies that the intestine develops the capacity to deal with increased carbohydrate loads by absorbing more carbohydrate in aggregate, although not per unit area (Figure 5). This will generate higher concentration peaks of carbohydrate in the splanchnic circulation following absorbable carbohydrate ingestion41,45 and higher rates of splanchnic blood flow in conscious animals46–48.

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