{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:07:42Z","timestamp":1760123262441,"version":"3.40.5"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["SNN134497"],"award-info":[{"award-number":["SNN134497"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Type 1 diabetes is a disease of the endocrine pancreas; however, it also affects exocrine function. Although most studies have examined the effects of diabetes on acinar cells, much less is known regarding ductal cells, despite their important protective function in the pancreas. Therefore, we investigated the effect of diabetes on ductal function. Diabetes was induced in wild\u2010type and cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice following an <jats:sc>i.p.<\/jats:sc> administration of streptozotocin. Pancreatic ductal fluid and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion were determined using fluid secretion measurements and fluorescence microscopy, respectively. The expression of ion transporters was measured by real\u2010time PCR and immunohistochemistry. Transmission electron microscopy was used for the morphological characterization of the pancreas. Serum secretin and cholecystokinin levels were measured by an enzyme\u2010linked immunosorbent assay. Ductal fluid and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion, CFTR activity, and the expression of CFTR, Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchanger\u20101, anoctamine\u20101 and aquaporin\u20101 were significantly elevated in diabetic mice. Acute or chronic glucose treatment did not affect HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion, but increased alkalizing transporter activity. Inhibition of CFTR significantly reduced HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion in both normal and diabetic mice. Serum levels of secretin and cholecystokinin were unchanged, but the expression of secretin receptors significantly increased in diabetic mice. Diabetes increases fluid and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion in pancreatic ductal cells, which is associated with the increased function of ion and water transporters, particularly CFTR.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15952-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>There is a lively interaction between the exocrine and endocrine pancreas not only under physiological conditions, but also under pathophysiological conditions<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The most common disease affecting the endocrine part is type\u20101 diabetes mellitus (T1DM), which is often associated with pancreatic exocrine insufficiency<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Compared with acinar cells, there is considerably less information regarding the effect of diabetes on pancreatic ductal epithelial cells, despite the fact that the large amount of fluid and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> produced by ductal cells is essential for maintaining normal pancreatic functions<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Ductal fluid and HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion increase in T1DM, in which increased cystic fibrosis transmembrane conductance regulator activation plays a central role.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We have identified a novel interaction between T1DM and ductal cells. Presumably, the increased ductal secretion represents a defence mechanism in the prevention of diabetes, but further studies are needed to clarify this issue.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285702","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T06:54:07Z","timestamp":1708671247000},"page":"1065-1083","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Role of CFTR in diabetes\u2010induced pancreatic ductal fluid and HCO<sub>3<\/sub><sup>\u2212<\/sup> secretion"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3650-837X","authenticated-orcid":false,"given":"Attila","family":"\u00c9bert","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy University of Szeged  Szeged Hungary"},{"name":"ELI ALPS ELI\u2010HU Non\u2010Proft Ltd  Szeged Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleon\u00f3ra","family":"G\u00e1l","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy University of Szeged  Szeged Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emese","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Translational Pancreatology Research Group, Interdisciplinary Center of Excellence for Research Development and Innovation University of Szeged  Szeged Hungary"},{"name":"Department of Health Sciences, Department of Theoretical and Integrative Health Sciences University of Debrecen  Debrecen Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Titanilla","family":"Sz\u00f6gi","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Szeged  Szeged Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-7259","authenticated-orcid":false,"given":"P\u00e9ter","family":"Hegyi","sequence":"additional","affiliation":[{"name":"Translational Pancreatology Research Group, Interdisciplinary Center of Excellence for Research Development and Innovation University of Szeged  Szeged Hungary"},{"name":"Institute for Translational Medicine, Szent\u00e1gothai Research Centre, Medical School University of P\u00e9cs  P\u00e9cs Hungary"},{"name":"Centre for Translational Medicine Semmelweis University  Budapest Hungary"},{"name":"Division of Pancreatic Diseases, Heart and Vascular Center Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2316-7247","authenticated-orcid":false,"given":"Vikt\u00f3ria","family":"Venglovecz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy University of Szeged  Szeged Hungary"},{"name":"Institute for Translational Medicine, Szent\u00e1gothai Research Centre, Medical School University of P\u00e9cs  P\u00e9cs Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"29","article-title":"The physiological roles of secretin and its receptor","volume":"1","author":"Afroze S.","year":"2013","journal-title":"Annals of Translational Medicine"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1627-9"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1986.sp003023"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.07.051"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.5R6640.2005"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.7.1008"},{"key":"e_1_2_5_8_1","first-page":"35","article-title":"Hormonal control of exocrine pancreatic secretion in the isolated intact rat pancreas","volume":"50","author":"Camello P. 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