Oxidative stress and impaired insulin secretion in cystic fibrosis pig pancreas

Yunxia O'Malley; Mitchell C. Coleman; Xingshen Sun; Junying Lei; Jianrong Yao; Casey F. Pulliam; Paige Kluz; Michael L. McCormick; Yaling Yi; Yumi Imai; John F. Engelhardt; Andrew W. Norris; Douglas R. Spitz; Aliye Uc

doi:10.1016/j.arres.2022.100040

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Oxidative stress and impaired insulin secretion in cystic fibrosis pig pancreas

Journal article

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Oxidative stress and impaired insulin secretion in cystic fibrosis pig pancreas

Yunxia O'Malley, Mitchell C. Coleman, Xingshen Sun, Junying Lei, Jianrong Yao, Casey F. Pulliam, Paige Kluz, Michael L. McCormick, Yaling Yi, Yumi Imai, …

Advances in Redox Research, Vol.5, p.100040

07/01/2022

DOI: 10.1016/j.arres.2022.100040

PMCID: PMC9328447

PMID: 35903252

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Abstract

Cystic fibrosis-related diabetes (CFRD) is one the most common comorbidities in cystic fibrosis (CF). Pancreatic oxidative stress has been postulated in the pathogenesis of CFRD, but no studies have been done to show an association. The main obstacle is the lack of suitable animal models and no immediate availability of pancreas tissue in humans. In the CF porcine model, we found increased pancreatic total glutathione (GSH), glutathione disulfide (GSSG), 3-nitrotyrosine- and 4-hydroxynonenal-modified proteins, and decreased copper zinc superoxide dismutase (CuZnSOD) activity, all indicative of oxidative stress. CF pig pancreas demonstrated increased DHE oxidation (as a surrogate marker of superoxide) in situ compared to non-CF and this was inhibited by a SOD-mimetic (GC4401). Catalase and glutathione peroxidase activities were not different between CF and non-CF pancreas. Isolated CF pig islets had significantly increased DHE oxidation, peroxide production, reduced insulin secretion in response to high glucose and diminished secretory index compared to non-CF islets. Acute treatment with apocynin or an SOD mimetic failed to restore insulin secretion. These results are consistent with the hypothesis that CF pig pancreas is under significant oxidative stress as a result of increased O2●− and peroxides combined with reduced antioxidant defenses against reactive oxygen species (ROS). We speculate that insulin secretory defects in CF may be due to oxidative stress.

Cystic Fibrosis

Oxidative Stress

Pancreas

Glutathione

Islet cells

Superoxide

Details

Title: Subtitle: Oxidative stress and impaired insulin secretion in cystic fibrosis pig pancreas
Creators: Yunxia O'Malley - University of Iowa
Mitchell C. Coleman - University of Iowa
Xingshen Sun - University of Iowa
Junying Lei - University of Iowa
Jianrong Yao - University of Iowa
Casey F. Pulliam - University of Iowa
Paige Kluz - University of Iowa
Michael L. McCormick - University of Iowa
Yaling Yi - University of Iowa
Yumi Imai
John F. Engelhardt - University of Iowa
Andrew W. Norris
Douglas R. Spitz - University of Iowa
Aliye Uc
Resource Type: Journal article
Publication Details: Advances in Redox Research, Vol.5, p.100040
DOI: 10.1016/j.arres.2022.100040
PMID: 35903252
PMCID: PMC9328447
NLM abbreviation: Adv Redox Res
ISSN: 2667-1379
Publisher: Elsevier
Grant note: DOI: 10.13039/100000069, name: National Institute of Arthritis and Musculoskeletal and Skin Diseases, award: AR070914; DOI: 10.13039/100000002, name: National Institutes of Health, award: DK090490, DK115791, RC2 DK124207; DOI: 10.13039/100000009, name: Foundation for the National Institutes of Health; DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: DK096518, DK097820, U01 DK108334, DK118752
Language: English
Date published: 07/01/2022
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Endocrinology and Diabetes; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Pathology; Orthopedics and Rehabilitation; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984267577202771

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