Structural and functional impact of cystic fibrosis on endocrine pancreatic innervation

Xingshen Sun; Yaling Yi; Shanming Hu; Gulnara Novbatova; Aliye Uc; Katie Larson Ode; John F Engelhardt; Andrew W Norris

doi:10.1042/CS20260182

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Structural and functional impact of cystic fibrosis on endocrine pancreatic innervation

Journal article

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Structural and functional impact of cystic fibrosis on endocrine pancreatic innervation

Xingshen Sun, Yaling Yi, Shanming Hu, Gulnara Novbatova, Aliye Uc, Katie Larson Ode, John F Engelhardt and Andrew W Norris

Clinical science (1979)

09/29/2026

DOI: 10.1042/CS20260182

PMID: 42734228

Appears in UI Libraries Support Open Access

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Abstract

In health, the autonomic nervous system modifies secretion of the islet hormones insulin, glucagon, and pancreatic polypeptide (PP). Uniquely, PP secretion is nearly fully dependent upon parasympathetic innervation. In people with cystic fibrosis (CF), physiological secretion of all three hormones is impaired, but the role of the autonomic nervous system in this dysfunction is unknown. 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 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.

neurodegeneration

glucagon

pancreatic beta cell

autonomic nervous system

pancreatic polypeptide

pancreatic islets

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Details

Title: Subtitle: Structural and functional impact of cystic fibrosis on endocrine pancreatic innervation
Creators: Xingshen Sun - University of Alabama at Birmingham
Yaling Yi - University of Alabama at Birmingham
Shanming Hu - University of Iowa
Gulnara Novbatova - University of Iowa
Aliye Uc - University of Iowa
Katie Larson Ode - University of Iowa
John F Engelhardt - University of Alabama at Birmingham
Andrew W Norris - University of Iowa
Resource Type: Journal article
Publication Details: Clinical science (1979)
DOI: 10.1042/CS20260182
PMID: 42734228
NLM abbreviation: Clin Sci (Lond)
ISSN: 0143-5221
eISSN: 1470-8736
Publisher: Portland Press
Language: English
Electronic publication date: 09/29/2026
Academic Unit: Endocrinology and Diabetes; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Biochemistry and Molecular Biology
Record Identifier: 9985230923802771

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