Article Text

Potassium and sodium dependent glucose transport: implications for cystic fibrosis
  1. A H BEESLEY,
  2. J HARDCASTLE,
  3. P T HARDCASTLE
  1. Department of Biomedical Science
  2. University of Sheffield
  3. Sheffield S10 2TN
  4. Department of Paediatrics
  5. Sheffield Children’s Hospital
  6. Sheffield S10 2TN
    1. C J TAYLOR
    1. Department of Biomedical Science
    2. University of Sheffield
    3. Sheffield S10 2TN
    4. Department of Paediatrics
    5. Sheffield Children’s Hospital
    6. Sheffield S10 2TN

      Statistics from Altmetric.com

      Editor,—In cystic fibrosis intestine there is an increase in the rate of sodium coupled glucose absorption,1 which exacerbates the characteristic luminal dehydration of this disease resulting from the failure of chloride secretion. The mechanism for the sodium dependent uptake of sugars from the small intestine is now well established, but early studies of its cation dependency revealed that replacement of external sodium with potassium had a greater inhibitory effect than replacement with urea or Tris.2 This was explained as competition between sodium and potassium for a common binding site on the glucose transporter and it was argued that intracellular potassium might therefore displace sodium and sugar from the carrier and promote further transport by returning the carrier to a conformation suitable for membrane recycling.2 Since it has recently been reported that cystic fibrosis enterocytes may possess higher intracellular potassium concentrations than non-cystic fibrosis cells,3 it is possible that enhanced sodium/glucose absorption in this disease could be a secondary effect of abnormalities in cellular potassium handling. The purpose of this study was to test whether potassium may have a direct effect on active sodium/glucose uptake using intestinal brush border membrane vesicles (BBMVs).

      BBMVs were prepared from rat jejunal mucosal scrapes using a magnesium precipitation technique.4 Human BBMVs were prepared in a similar manner, using operative sections of distal ileum taken from patients presenting with intestinal obstruction. All human tissues were morphologically normal and each specimen was obtained from an individual patient. BBMVs were loaded with a buffer containing additional potassium chloride or osmotically equivalent amounts of potassium gluconate, or mannitol. Glucose uptakes were determined after 60 second incubations in a buffer containing 100 mM sodium gluconate, 100 μM 3H-d-glucose plus additional potassium chloride, potassium gluconate, or mannitol. Active (sodium dependent) glucose transport was calculated from the uptake differences in the presence or absence of phlorrhizin (250 μM).

      Active glucose uptake into rat BBMVs was significantly inhibited in the presence of 105 mM external potassium gluconate, but was stimulated when 105 mM potassium gluconate was present internally (fig 1A). This stimulation was also seen when 100 mM potassium chloride was present bilaterally, indicating that the electrogenic movement of potassium is not responsible for these changes. A similar pattern was observed using human BBMVs (fig 1B). These data are consistent with the concept of competition between sodium and potassium for the binding site on the sodium/glucose cotransporter and support the possibility that the enhanced sodium/glucose absorption in cystic fibrosis intestine may be partly attributable to defects in cellular potassium handling.

      Figure 1

      Effect of internal/external potassium chloride (KCl; 100 mM), potassium gluconate (KG; 105 mM), or mannitol (M; 178 mM) on active glucose uptake into rat (A) or human (B) BBMVs; *p <0.05 v mannitol only controls (Student’s paired t test or one way analysis of variance as appropriate).The data indicated by shaded bars were obtained in a different experimental series from data denoted by open bars.

      References

      View Abstract

      Request permissions

      If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.