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Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients
Published on: February 11, 2017
Intestinal transport in cystic fibrosis (CF)
J Hardcastle1, C J Taylor, P T Hardcastle
1Department of Biomedical Science, University Western Bank, Sheffield.
Insights
Cystic fibrosis (CF) intestinal tissues show impaired chloride secretion but enhanced glucose absorption. This study highlights distinct ion transport defects in the CF jejunum, impacting nutrient absorption.
Area of Science:
- Gastroenterology
- Physiology
- Genetics
Background:
- Cystic fibrosis (CF) is a genetic disorder affecting multiple organs.
- Intestinal dysfunction is a recognized complication of CF.
- Understanding ion transport in the CF jejunum is crucial for managing gastrointestinal symptoms.
Purpose of the Study:
- To investigate ion transport mechanisms in jejunal biopsies from CF patients.
- To assess chloride secretion and glucose absorption in CF intestinal tissue.
- To identify specific defects in electrogenic ion transport in CF.
Main Methods:
- Utilized short-circuit current (SCC) measurements in jejunal biopsies.
- Assessed net electrogenic ion transport as an index of function.
- Compared ion transport responses between CF and control tissues.
Main Results:
- CF tissues demonstrated a failure in stimulated chloride (Cl-) secretion.
- Control tissues showed normal increases in SCC with Cl- secretagogues.
- CF tissues exhibited an enhanced Na(+)-linked glucose absorption compared to controls.
Conclusions:
- Intestinal Cl- secretion is impaired in cystic fibrosis patients.
- Enhanced active glucose absorption occurs in the CF jejunum.
- These findings reveal specific ion transport abnormalities in the CF intestine.
Abstract:
Ion transport was measured in jejunal biopsies using short-circuit current (SCC) as an index of net electrogenic ion transport. Increases in SCC associated with stimulation of Cl- secretion were observed in control tissues, but CF tissues did not exhibit such a response, indicating a failure of intestinal Cl- secretion. The rise in SCC associated with Na(+)-linked glucose absorption was greater in CF tissues than in controls, reflecting an enhanced active absorption of glucose.
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