Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA112

Poster Communications

Genetic deletion of the Slc26a9 anion transporter results in reduced pancreatic fluid secretion and impaired glucose tolerance in young female mice

T. Li1,2, G. di Stefano1, B. Riederer1, G. Raza3, D. Römermann1, P. Pallagi4, M. Soleimani5, K. Herzig3, U. E. Seidler1

1. Gastroenterology, Hannover Medical School, Hannover, Lower Saxony, Germany. 2. Gastrointestinal Surgery, Zunyi Medical College, Zunyi, China. 3. Institute of Biomedicine and Biocenter of Oulu, Oulu University, Oulu, Finland. 4. Institute of Theoretical Medicine, University of Szeged, Szeged, Hungary. 5. Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United Kingdom.

Background: Slc26a9 is a member of the Slc26 multifunctional anion transporter family. In expression systems, it interacts with CFTR and may enhance or inhibit CFTR function, depending on the expression system. Polymorphisms in Slc26a9 are associated with an increased incidence of diabetes in cystic fibrosis patients. Aim: We investigated the expression of Slc26a9 in the pancreas and elucidated its potential role in pancreatic ductal electrolyte and fluid secretion and in pancreatic endocrine function. Methods and Results: The mRNA expression of Slc26a9 was low in pancreatic parenchyma but 20-fold higher in microdissected pancreatic ducts. No Slc26a9 mRNA expression was detected in the liver, while bile ducts displayed low Slc26a9 expression. Pancreatic and biliary fluid and bicarbonate secretion were assessed in isoflurane (1.3-1.8%) anesthetized, artificially ventilated Slc29-/- and age- and sex-matched wildtype (WT) littermates. To test pancreatic endocrine function, blood glucose levels were measured after an i.p glucose bolus over a period of 2 hours. Significantly reduced basal as well as secretin-stimulated pancreatic fluid secretory rates were observed in young adult (6-8 weeks) female Slc26a9-/- mice, with no difference in the bicarbonate secretory rates. In young male mice, as well as male and female aged mice (>1 year), no significant difference in pancreatic ion secretion was observed. Blood glucosa levels declined slightly but significantly slower after 2g/kg i.p. glucose bolus in Slc29a9-/- female mice. No difference in peripheral insulin resistence was observed in Slc26a9-/- compared to sex- and age- matched controls. Biliary fluid and bicarbonate secretion were not affected by loss of Slc26a9 expression. Conclusions: Deletion of Slc26a9 is associated with a reduction in pancreatic fluid secretion and impaired glucose tolerance in young female mice. The results underline the importance of Slc26a9 in pancreatic physiology particularly at young age.

Where applicable, experiments conform with Society ethical requirements