PT12. - IMPROVED GLUCOSE ABSORPTION THROUGH ENHANCED SLGT1 ACTIVITY MAY CONTRIBUTE TO INTESTINAL ADAPTATION IN PATIENTS WITH SHORT BOWEL SYNDROME.
PT12.
IMPROVED GLUCOSE ABSORPTION THROUGH ENHANCED SLGT1 ACTIVITY MAY CONTRIBUTE TO INTESTINAL ADAPTATION IN PATIENTS WITH SHORT BOWEL SYNDROME.
L. De Meyere1,2,*, A. Viaene1, A. Verbiest1,2, J. Tόth1, L. Timmermans2, K. Geboers2, L. Wauters1,2, R. Farré1, T. Vanuytsel1,2
1TARGID, KU Leuven, 2LIFT, UZ Leuven, Leuven, Belgium
Rationale: Short bowel syndrome (SBS) is the most common cause of chronic intestinal failure. Based on animal data we hypothesize that patients with SBS have an altered barrier function with altered ion secretion playing a role in fluid and electrolyte homeostasis.
Methods: Patients with stable (>1y) SBS (n=11) and controls (n=17) were included. Duodenal and sigmoid biopsies were mounted in Ussing chambers. Transepithelial electrical resistance (TEER) was calculated and the paracellular flux of a 4kDa labeled dextran was assessed. The short-circuit current (Isc) was measured after which the effect of amiloride (100 µM, luminal), bethanechol (10 mM, basolateral, colon only) and glucose (15mM, luminal, duodenum only) was measured, each for 10 min.
Results: Intestinal permeability was similar between patients and controls. However, despite a similar baseline ISc, the glucose-induced increase in Isc in the duodenum was more pronounced in SBS. Moreover, a significantly lower baseline Isc was observed in the sigmoid in SBS and the normal reduction in Isc with amiloride in controls was not observed in SBS. Finally, the bethanechol-induced increase in Isc in the sigmoid was reduced in SBS.
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Conclusion: Patients with SBS show reduced Na+ absorption and reduced Cl- secretion in the colon, as observed by the lower basal Isc, and the altered response to amiloride and bethanechol. The higher glucose-induced Isc in the duodenum indicates an increase of glucose and Na+ uptake through the Na+-glucose cotransporter SGLT1 in patients with SBS, which may contribute to the natural intestinal adaptation after resection.
Disclosure of Interest: L. De Meyere: None declared, A. Viaene: None declared, A. Verbiest: None declared, J. Tόth: None declared, L. Timmermans: None declared, K. Geboers: None declared, L. Wauters: None declared, R. Farré: None declared, T. Vanuytsel Grant / Research Support from: TV has received research grants from Takeda and VectivBio., Consultant for: TV has provided clinical advice to Baxter, Shire, Takeda, VectivBio, Zealand Pharma., Speakers Bureau of: TV has served on the speaker bureau for Fresenius Kabi, Remedus, Takeda, and VectivBio