Chronic continuous exenatide infusion does not cause pancreatic inflammation and ductal hyperplasia in non-human primates.

Details

Serval ID
serval:BIB_7373E1934ACB
Type
Article: article from journal or magazin.
Collection
Publications
Title
Chronic continuous exenatide infusion does not cause pancreatic inflammation and ductal hyperplasia in non-human primates.
Journal
American Journal of Pathology
Author(s)
Fiorentino T.V., Owston M., Abrahamian G., La Rosa S., Marando A., Perego C., Di Cairano E.S., Finzi G., Capella C., Sessa F., Casiraghi F., Paez A., Adivi A., Davalli A., Fiorina P., Guardado Mendoza R., Comuzzie A.G., Sharp M., DeFronzo R.A., Halff G., Dick E.J., Folli F.
ISSN
1525-2191 (Electronic)
ISSN-L
0002-9440
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
185
Number
1
Pages
139-150
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67-positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67-positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67-positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30-positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates.
Keywords
Amylases/blood, Animals, Apoptosis, Female, Hyperplasia, Hypoglycemic Agents/administration & dosage, Hypoglycemic Agents/adverse effects, Immunohistochemistry, Inflammation/pathology, Infusions, Intravenous, Insulin Resistance, Ki-67 Antigen/metabolism, Male, Microscopy, Fluorescence, Pancreas, Exocrine/metabolism, Pancreas, Exocrine/pathology, Pancreatic Ducts/cytology, Pancreatic Ducts/pathology, Papio, Peptides/administration & dosage, Peptides/adverse effects, Phenotype, Venoms/administration & dosage, Venoms/adverse effects
Pubmed
Web of science
Open Access
Yes
Create date
06/09/2016 11:55
Last modification date
20/08/2019 14:31
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