PMID- 33994067
OWN - NLM
STAT- MEDLINE
DCOM- 20220105
LR  - 20220802
IS  - 1424-3911 (Electronic)
IS  - 1424-3903 (Print)
IS  - 1424-3903 (Linking)
VI  - 21
IP  - 5
DP  - 2021 Aug
TI  - Acute pancreatitis-induced islet dysfunction in ferrets.
PG  - 839-847
LID - S1424-3903(21)00147-2 [pii]
LID - 10.1016/j.pan.2021.04.008 [doi]
AB  - 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. METHODS: We 
      injected ferrets with intraperitoneal cerulein (50 mug/kg, 9 hourly injections) or 
      saline. Blood samples were collected for glucose (0, 4, 8, 12, 24h); TNF-alpha, 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. RESULTS: Cerulein-injected ferrets exhibited mild pancreatic 
      edema, neutrophil infiltration, and elevations in serum amylase, lipase, TNF-alpha, 
      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. CONCLUSIONS: 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.
CI  - Copyright (c) 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.
FAU - Yi, Yaling
AU  - Yi Y
AD  - Department of Anatomy and Cell Biology, Iowa City, IA, USA.
FAU - Sun, Xingshen
AU  - Sun X
AD  - Department of Anatomy and Cell Biology, Iowa City, IA, USA.
FAU - Liang, Bo
AU  - Liang B
AD  - Department of Anatomy and Cell Biology, Iowa City, IA, USA.
FAU - He, Nan
AU  - He N
AD  - Department of Anatomy and Cell Biology, Iowa City, IA, USA.
FAU - Gibson-Corley, Katherine N
AU  - Gibson-Corley KN
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, TN, USA.
FAU - Norris, Andrew W
AU  - Norris AW
AD  - Fraternal Order of Eagles Diabetes Research Center, Iowa City, IA, USA; 
      Department of Pediatrics, lowa City, IA, USA; Department of Biochemistry, Iowa 
      City, IA, USA.
FAU - Engelhardt, John F
AU  - Engelhardt JF
AD  - Department of Anatomy and Cell Biology, Iowa City, IA, USA; Fraternal Order of 
      Eagles Diabetes Research Center, Iowa City, IA, USA.
FAU - Uc, Aliye
AU  - Uc A
AD  - Fraternal Order of Eagles Diabetes Research Center, Iowa City, IA, USA; 
      Department of Pediatrics, lowa City, IA, USA; Department of Radiation Oncology; 
      University of Iowa, Iowa City, IA, USA. Electronic address: aliye-uc@uiowa.edu.
LA  - eng
GR  - R01 DK115791/DK/NIDDK NIH HHS/United States
GR  - R01 DK118752/DK/NIDDK NIH HHS/United States
GR  - 27307C0010/ES/NIEHS NIH HHS/United States
GR  - RC2 DK124207/DK/NIDDK NIH HHS/United States
GR  - P30 DK054759/DK/NIDDK NIH HHS/United States
GR  - U01 DK108334/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20210511
PL  - Switzerland
TA  - Pancreatology
JT  - Pancreatology : official journal of the International Association of 
      Pancreatology (IAP) ... [et al.]
JID - 100966936
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 888Y08971B (Ceruletide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-92-5 (Glucagon)
RN  - EC 3.1.1.3 (Lipase)
RN  - EC 3.2.1.- (Amylases)
SB  - IM
MH  - Acute Disease
MH  - Amylases
MH  - Animals
MH  - Blood Glucose
MH  - Ceruletide/toxicity
MH  - Ferrets
MH  - Gastric Inhibitory Polypeptide
MH  - Glucagon
MH  - Glucagon-Like Peptide 1
MH  - Humans
MH  - *Hyperglycemia
MH  - Insulin
MH  - *Insulin Resistance
MH  - Interleukin-6
MH  - Lipase
MH  - *Pancreatitis/chemically induced/veterinary
MH  - Tumor Necrosis Factor-alpha
PMC - PMC8355067
MID - NIHMS1704920
OTO - NOTNLM
OT  - Glucagon
OT  - Glucose intolerance
OT  - Incretins
OT  - Insulin
OT  - Pancreatitis
COIS- Declaration of competing interest Dr. Aliye Uc is an Associate Editor of 
      Pancreatology, Subboard Chair of American Board of Pediatrics and Consultant for 
      Cystic Fibrosis Foundation. All others authors declare no conflict of interests.
EDAT- 2021/05/18 06:00
MHDA- 2022/01/06 06:00
PMCR- 2022/08/01
CRDT- 2021/05/17 05:42
PHST- 2021/01/13 00:00 [received]
PHST- 2021/04/22 00:00 [revised]
PHST- 2021/04/24 00:00 [accepted]
PHST- 2021/05/18 06:00 [pubmed]
PHST- 2022/01/06 06:00 [medline]
PHST- 2021/05/17 05:42 [entrez]
PHST- 2022/08/01 00:00 [pmc-release]
AID - S1424-3903(21)00147-2 [pii]
AID - 10.1016/j.pan.2021.04.008 [doi]
PST - ppublish
SO  - Pancreatology. 2021 Aug;21(5):839-847. doi: 10.1016/j.pan.2021.04.008. Epub 2021 
      May 11.