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We thus examined PP secretion and pancreatic neuronal immunostaining in humans and ferrets with CF. Both young humans and ferrets with CF had greatly impaired PP secretion, despite an abundance of islet PP cells and intact PP secretion from perifused CF ferret islets. Pan-neuronal staining in the pancreas was nearly absent from CF humans and of aberrant morphology and distribution in CF ferrets. Parasympathetic neuronal staining was nearly absent in both ferret and human CF pancreata. When exocrine pancreatic disease was delayed until after the first month of life by administering a CFTR modulator in CFTRG551D homozygous ferrets, there was preservation of pancreatic neuronal markers and restoration of PP secretory responsiveness to oral glucose. We conclude that the CF pancreas is impacted by a loss and remodeling of its innervation, secondary to early-life pancreatic disease, likely contributing to impaired islet hormone secretion.<\/jats:p>","DOI":"10.1042\/cs20260182","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:27:39Z","timestamp":1789385259000},"page":"2179-2197","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural and functional impact of cystic fibrosis on endocrine pancreatic innervation"],"prefix":"10.1042","volume":"140","author":[{"given":"Xingshen","family":"Sun","sequence":"first","affiliation":[{"name":"1Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Yi","sequence":"additional","affiliation":[{"name":"1Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanming","family":"Hu","sequence":"additional","affiliation":[{"name":"2Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnara","family":"Novbatova","sequence":"additional","affiliation":[{"name":"2Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2004-5743","authenticated-orcid":false,"given":"Aliye","family":"Uc","sequence":"additional","affiliation":[{"name":"2Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A."},{"name":"3Fraternal Order of Eagle Diabetes Research Center, University of Iowa, Iowa City, IA 52242, U.S.A."},{"name":"4Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1086-9135","authenticated-orcid":false,"given":"Katie\u00a0Larson","family":"Ode","sequence":"additional","affiliation":[{"name":"2Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A."},{"name":"3Fraternal Order of Eagle Diabetes Research Center, University of Iowa, Iowa City, IA 52242, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2389-9277","authenticated-orcid":false,"given":"John\u00a0F.","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"1Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-9543","authenticated-orcid":false,"given":"Andrew\u00a0W.","family":"Norris","sequence":"additional","affiliation":[{"name":"2Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A."},{"name":"3Fraternal Order of Eagle Diabetes Research Center, University of Iowa, Iowa City, IA 52242, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"2026092904515805900_B1","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.jcf.2024.02.010","article-title":"Early onset of abnormal glucose tolerance in patients with cystic fibrosis: a systematic review and meta-analysis","volume":"23","author":"K\u00e9ri","year":"2024","journal-title":"J. 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