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Polymorphisms in Slc26a9 are associated with an increased incidence of meconium ileus and diabetes in cystic fibrosis patients. We investigated the expression of Slc26a9 in the murine pancreatic ducts, islets and parenchyma, and elucidated its role in pancreatic ductal electrolyte and fluid secretion and endocrine function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pancreatic Slc26a9 and CFTR mRNA expression, fluid and bicarbonate secretion were assessed in <jats:italic>slc26a9<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice and their age\u2010 and sex\u2010matched wild\u2010type (wt) littermates. Glucose and insulin tolerance tests were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with stomach, the mRNA expression of Slc26a9 was low in pancreatic parenchyma, 20\u2010fold higher in microdissected pancreatic ducts than parenchyma, and very low in islets. CFTR mRNA was ~10 fold higher than Slc26a9 mRNA expression in each pancreatic cell type. Significantly reduced pancreatic fluid secretory rates and impaired glucose tolerance were observed in female <jats:italic>slc26a9<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, whereas alterations in male mice did not reach statistical significance. No significant difference was observed in peripheral insulin resistance in <jats:italic>slc26a9<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> compared to sex\u2010 and aged\u2010matched wt controls. In contrast, isolated <jats:italic>slc26a9<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> islets in short term culture displayed no difference in insulin content, but a significantly reduced glucose\u2010stimulated insulin secretion compared to age\u2010 and sex\u2010matched wt islets, suggesting that the impaired glucose tolerance in the absence of Slc26a9 expression these is a pancreatic defect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Deletion of Slc26a9 is associated with a reduction in pancreatic fluid secretion and impaired glucose tolerance in female mice. The results underline the importance of Slc26a9 in pancreatic physiology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13729","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T16:00:57Z","timestamp":1631721657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hydrokinetic pancreatic function and insulin secretion are moduled by Cl<sup>\u2212<\/sup> uniporter Slc26a9 in mice"],"prefix":"10.1111","volume":"234","author":[{"given":"T.","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Hannover Medical School Hannover Germany"},{"name":"Department of Thyroid and Breast Surgery Affiliated Hospital of Zunyi Medical University Zunyi P.R. 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