Journal article
Acute pancreatitis-induced islet dysfunction in ferrets
Pancreatology : official journal of the International Association of Pancreatology (IAP), Vol.21(5), pp.839-847
08/2021
DOI: 10.1016/j.pan.2021.04.008
PMCID: PMC8355067
PMID: 33994067
Abstract
/Objectives: The pathogenesis of hyperglycemia during acute pancreatitis (AP) remains unknown due to inaccessibility of human tissues and lack of animal models. We aimed to develop an animal model to study the mechanisms of hyperglycemia and impaired glucose tolerance in AP.
We injected ferrets with intraperitoneal cerulein (50 μg/kg, 9 hourly injections) or saline. Blood samples were collected for glucose (0, 4, 8, 12, 24h); TNF-α, IL-6 (6h); amylase, lipase, insulin, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) (24h). Animals underwent oral glucose tolerance test (OGTT), mixed meal tolerance test (MMTT) at 24h or 3 months, followed by harvesting pancreas for histopathology and immunostaining.
Cerulein-injected ferrets exhibited mild pancreatic edema, neutrophil infiltration, and elevations in serum amylase, lipase, TNF-α, IL-6, consistent with AP. Plasma glucose was significantly higher in ferrets with AP at all time points. Plasma glucagon, GLP-1 and PP were significantly higher in cerulein-injected animals, while plasma insulin was significantly lower compared to controls. OGTT and MMTT showed abnormal glycemic responses with higher area under the curve. The hypoglycemic response to insulin injection was completely lost, suggestive of insulin resistance. OGTT showed low plasma insulin; MMTT confirmed low insulin and GIP; abnormal OGTT and MMTT responses returned to normal 3 months after cerulein injection.
Acute cerulein injection causes mild acute pancreatitis in ferrets and hyperglycemia related to transient islet cell dysfunction and insulin resistance. The ferret cerulein model may contribute to the understanding of hyperglycemia in acute pancreatitis.
Details
- Title: Subtitle
- Acute pancreatitis-induced islet dysfunction in ferrets
- Creators
- Yaling Yi - University of IowaXingshen Sun - University of IowaBo Liang - University of IowaNan He - University of IowaKatherine N. Gibson-Corley - Vanderbilt University Medical CenterAndrew W. Norris - University of IowaJohn F. Engelhardt - University of IowaAliye Uc - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Pancreatology : official journal of the International Association of Pancreatology (IAP), Vol.21(5), pp.839-847
- DOI
- 10.1016/j.pan.2021.04.008
- PMID
- 33994067
- PMCID
- PMC8355067
- NLM abbreviation
- Pancreatology
- ISSN
- 1424-3903
- eISSN
- 1424-3911
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: 75N2019C00010, P30 DK054759, U01 DK108334, R01DK118752, RC2 DK124207, R01 DK115791; DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: 75N2019C00010, P30 DK054759, U01 DK108334, R01DK118752, RC2 DK124207, R01 DK115791
- Language
- English
- Date published
- 08/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Endocrinology and Diabetes; Anatomy and Cell Biology; Stead Family Department of Pediatrics; The University of Iowa Institute for Vision Research; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984284339002771
Metrics
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