Acute pancreatitis-induced islet dysfunction in ferrets |
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| Institution: | 1. Department of Anatomy and Cell Biology, Iowa City, IA, USA;2. Fraternal Order of Eagles Diabetes Research Center, Iowa City, IA, USA;3. Department of Pediatrics, lowa City, IA, USA;4. Department of Biochemistry, Iowa City, IA, USA;5. Department of Radiation Oncology; University of Iowa, Iowa City, IA, USA;6. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA;1. Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson School of Medicine, New Brunswick, NJ, United States;2. Division of Gastroenterology and Hepatology, John H. Stroger Cook County Hospital, Chicago, IL, United States;3. Department of Gastroenterology, BIDMC, Boston, United States;4. Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, United States;5. Division of Gastroenterology and Hepatology, Fox Chase Cancer Center, Philadelphia, United States;6. Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, United States;1. Cedars Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA;2. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA;3. Center for Research on Healthcare Data Center, University of Pittsburgh, Pittsburgh, PA, USA;4. Mercy Clinic Gastroenterology, St. Louis, MO, USA;5. Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;6. Aurora St. Luke''s Medical Center, Milwaukee, WI, USA;7. Gastroenterology Associates, Richmond, VA, USA;8. Pancreatitis Center, Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;9. Division of Gastroenterology and Hepatology, University of Alabama Birmingham, AL, USA;10. Gastro Health, Baptist Health, Miami, FL, USA;1. Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;2. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;3. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;4. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;5. Evolution of Cancer, Leukemia and Immunity Post Stem Cell Transplant (ECLIPSE), The University of Texas MD Anderson Cancer Center, Houston, TX, USA;1. Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan;1. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea;2. Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea;3. Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea;4. Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea |
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| Abstract: | Background/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.MethodsWe 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.ResultsCerulein-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.ConclusionsAcute 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. |
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| Keywords: | Pancreatitis Glucose intolerance Insulin Glucagon Incretins |
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