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

Teresa Vanessa Fiorentino, Michael Owston, Gregory Abrahamian, Stefano La Rosa, Alessandro Marando, Carla Perego, Eliana S. Di Cairano, Giovanna Finzi, Carlo Capella, Fausto Sessa, Francesca Casiraghi, Ana Paez, Ashwin Adivi, Alberto Davalli, Paolo Fiorina, Rodolfo Guardado Mendoza, Anthony G. Comuzzie, Mark Sharp, Ralph A. Defronzo, Glenn Halff & 2 others Edward J. Dick, Franco Folli

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)139-150
Number of pages12
JournalAmerican Journal of Pathology
Volume185
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Primates
Hyperplasia
Inflammation
Exocrine Pancreas
Acinar Cells
Cell Count
Fluorescent Antibody Technique
Therapeutics
Papio hamadryas
Cell Transdifferentiation
exenatide
Staining and Labeling
Pancreatectomy
Papio
Pancreatitis
Cell Differentiation
Immunohistochemistry
Insulin
Phenotype

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Chronic continuous exenatide infusion does not cause pancreatic inflammation and ductal hyperplasia in non-human primates. / Fiorentino, Teresa Vanessa; Owston, Michael; Abrahamian, Gregory; La Rosa, Stefano; Marando, Alessandro; Perego, Carla; Di Cairano, Eliana S.; Finzi, Giovanna; Capella, Carlo; Sessa, Fausto; Casiraghi, Francesca; Paez, Ana; Adivi, Ashwin; Davalli, Alberto; Fiorina, Paolo; Guardado Mendoza, Rodolfo; Comuzzie, Anthony G.; Sharp, Mark; Defronzo, Ralph A.; Halff, Glenn; Dick, Edward J.; Folli, Franco.

In: American Journal of Pathology, Vol. 185, No. 1, 01.01.2015, p. 139-150.

Research output: Contribution to journalArticle

Fiorentino, TV, Owston, M, Abrahamian, G, La Rosa, S, Marando, A, Perego, C, Di Cairano, ES, Finzi, G, Capella, C, Sessa, F, Casiraghi, F, Paez, A, Adivi, A, Davalli, A, Fiorina, P, Guardado Mendoza, R, Comuzzie, AG, Sharp, M, Defronzo, RA, Halff, G, Dick, EJ & Folli, F 2015, 'Chronic continuous exenatide infusion does not cause pancreatic inflammation and ductal hyperplasia in non-human primates', American Journal of Pathology, vol. 185, no. 1, pp. 139-150. https://doi.org/10.1016/j.ajpath.2014.09.009
Fiorentino, Teresa Vanessa ; Owston, Michael ; Abrahamian, Gregory ; La Rosa, Stefano ; Marando, Alessandro ; Perego, Carla ; Di Cairano, Eliana S. ; Finzi, Giovanna ; Capella, Carlo ; Sessa, Fausto ; Casiraghi, Francesca ; Paez, Ana ; Adivi, Ashwin ; Davalli, Alberto ; Fiorina, Paolo ; Guardado Mendoza, Rodolfo ; Comuzzie, Anthony G. ; Sharp, Mark ; Defronzo, Ralph A. ; Halff, Glenn ; Dick, Edward J. ; Folli, Franco. / Chronic continuous exenatide infusion does not cause pancreatic inflammation and ductal hyperplasia in non-human primates. In: American Journal of Pathology. 2015 ; Vol. 185, No. 1. pp. 139-150.
@article{3bc75eee17cd4284b874f070a1aa6c26,
title = "Chronic continuous exenatide infusion does not cause pancreatic inflammation and ductal hyperplasia in non-human primates",
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.",
author = "Fiorentino, {Teresa Vanessa} and Michael Owston and Gregory Abrahamian and {La Rosa}, Stefano and Alessandro Marando and Carla Perego and {Di Cairano}, {Eliana S.} and Giovanna Finzi and Carlo Capella and Fausto Sessa and Francesca Casiraghi and Ana Paez and Ashwin Adivi and Alberto Davalli and Paolo Fiorina and {Guardado Mendoza}, Rodolfo and Comuzzie, {Anthony G.} and Mark Sharp and Defronzo, {Ralph A.} and Glenn Halff and Dick, {Edward J.} and Franco Folli",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.ajpath.2014.09.009",
language = "English",
volume = "185",
pages = "139--150",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Chronic continuous exenatide infusion does not cause pancreatic inflammation and ductal hyperplasia in non-human primates

AU - Fiorentino, Teresa Vanessa

AU - Owston, Michael

AU - Abrahamian, Gregory

AU - La Rosa, Stefano

AU - Marando, Alessandro

AU - Perego, Carla

AU - Di Cairano, Eliana S.

AU - Finzi, Giovanna

AU - Capella, Carlo

AU - Sessa, Fausto

AU - Casiraghi, Francesca

AU - Paez, Ana

AU - Adivi, Ashwin

AU - Davalli, Alberto

AU - Fiorina, Paolo

AU - Guardado Mendoza, Rodolfo

AU - Comuzzie, Anthony G.

AU - Sharp, Mark

AU - Defronzo, Ralph A.

AU - Halff, Glenn

AU - Dick, Edward J.

AU - Folli, Franco

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84918828271&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918828271&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2014.09.009

DO - 10.1016/j.ajpath.2014.09.009

M3 - Article

VL - 185

SP - 139

EP - 150

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -