Journal article
Survival in a bad neighborhood: pancreatic islets in cystic fibrosis
Journal of endocrinology, Vol.241(1), pp.R35-R50
04/2019
DOI: 10.1530/JOE-18-0468
PMID: 30759072
Abstract
In cystic fibrosis (CF), ductal plugging and acinar loss result in rapid decline of exocrine pancreatic function. This destructive process results in remodeled islets, with only a modest reduction in insulin-producing β cells. However, β-cell function is profoundly impaired, with decreased insulin release and abnormal glucose tolerance being present even in infants with CF. Ultimately, roughly half the CF subjects develop diabetes (termed CF-related diabetes (CFRD)). Importantly, CFRD increases CF morbidity and mortality via worsening catabolism and pulmonary disease. Current accepted treatment options for CFRD are aimed at insulin replacement, thereby improving glycemia as well as preventing nutritional losses and lung decline. CFRD is a unique form of diabetes with a distinct pathophysiology that is as yet incompletely understood. Recent studies highlight emerging areas of interest. First, islet inflammation and lymphocyte infiltration are common even in young children with CF and may contribute to β-cell failure. Second, controversy exists in the literature regarding the presence/importance of β-cell intrinsic functions of CFTR and its direct role in modulating insulin release. Third, loss of the CF transmembrane conductance regulator (CFTR) from pancreatic ductal epithelium, the predominant site of its synthesis, results in paracrine effects that impair insulin release. Finally, the degree of β-cell loss in CFRD does not appear sufficient to explain the deficit in insulin release. Thus, it may be possible to enhance the function of the remaining β-cells using strategies such as targeting islet inflammation or ductal CFTR deficiency to effectively treat or even prevent CFRD.
Details
- Title: Subtitle
- Survival in a bad neighborhood: pancreatic islets in cystic fibrosis
- Creators
- Andrew W Norris - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USAKatie Larson Ode - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USALina Merjaneh - Division of Endocrinology & Diabetes, Seattle Children’s Hospital, Seattle, Washington, USASrinath Sanda - Diabetes Center, University of California San Francisco, San Francisco, California, USAYaling Yi - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USAXingshen Sun - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USAJohn F Engelhardt - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USARebecca L Hull - Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington, USA
- Resource Type
- Journal article
- Publication Details
- Journal of endocrinology, Vol.241(1), pp.R35-R50
- Publisher
- Bioscientifica Ltd
- DOI
- 10.1530/JOE-18-0468
- PMID
- 30759072
- ISSN
- 0022-0795
- eISSN
- 1479-6805
- Alternative title
- Islet failure in cystic fibrosis
- Language
- English
- Date published
- 04/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Endocrinology and Diabetes; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Radiation Oncology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984024550602771
Metrics
15 Record Views