Small intestinal glucose absorption in cystic fibrosis: a study in human and transgenic ΔF508 cystic fibrosis mouse tissues

  • Hardcastle J
  • Harwood M
  • Taylor C
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Abstract

Intestinal transport is disturbed in cystic fibrosis (CF), with both defective Cl− secretion and changes in absorption being reported. We have examined the effects of the disease on Na+-dependent glucose absorption by the small intestine. Active glucose absorption was monitored as changes in short-circuit current (SCC) in intact and stripped intestinal sheets from normal (Swiss) and transgenic CF (Cftrtm 1 Eur and Cftrtm 2 Cam) mice with the ΔF508 mutation, and in jejunal biopsies from children with CF and normal controls. Na+-dependent glucose uptake at the luminal membrane was measured in brush-border membrane vesicles (BBMVs). Intact and stripped sheets of jejunum and midintestine from Swiss mice exhibited a concentration-dependent increase in SCC with glucose. Apparent Km values were similar in the two preparations, but the apparent Vmax was greater in stripped sheets. This difference was not due to a loss of neural activity in stripped sheets as tetrodotoxin did not influence the glucose-induced SCC in intact sheets. Similar results were observed in stripped sheets of jejunum and mid-intestine from wild-type Cftrtm 1 Eur mice, but in tissues from CF mice the apparent Vmax value was reduced significantly. A lower Vmax was also obtained in intact sheets of mid-intestine from CF (Cftrtm 2 Cam) mice. Jejunal biopsies from CF patients however, exhibited an enhanced glucose-dependent rise in SCC. Na+-dependent uptake by BBMVs from CF (Cftrtm 1 Eur) mice was not reduced compared with wild-type and Swiss BBMVs. It was concluded that, in contrast to human intestine, intestinal glucose absorption was reduced in transgenic mouse models of CF with the ΔF508 mutation, but that this could not be detected in an isolated preparation of brush-border membranes. Transgenic mouse models of CF may not accurately reflect all aspects of intestinal dysfunction in the human disease.

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Hardcastle, J., Harwood, M. D., & Taylor, C. J. (2010). Small intestinal glucose absorption in cystic fibrosis: a study in human and transgenic ΔF508 cystic fibrosis mouse tissues. Journal of Pharmacy and Pharmacology, 56(3), 329–338. https://doi.org/10.1211/0022357022863

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