Exenatide regulates pancreatic islet integrity and insulin sensitivity in the nonhuman primate baboon Papio hamadryas.
Détails
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Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_893519A0D48A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Exenatide regulates pancreatic islet integrity and insulin sensitivity in the nonhuman primate baboon Papio hamadryas.
Périodique
JCI insight
ISSN
2379-3708 (Electronic)
ISSN-L
2379-3708
Statut éditorial
Publié
Date de publication
17/10/2019
Peer-reviewed
Oui
Volume
4
Numéro
20
Pages
e93091
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
The glucagon-like peptide-1 receptor agonist exenatide improves glycemic control by several and not completely understood mechanisms. Herein, we examined the effects of chronic intravenous exenatide infusion on insulin sensitivity, β cell and α cell function and relative volumes, and islet cell apoptosis and replication in nondiabetic nonhuman primates (baboons). At baseline, baboons received a 2-step hyperglycemic clamp followed by an l-arginine bolus (HC/A). After HC/A, baboons underwent a partial pancreatectomy (tail removal) and received a continuous exenatide (n = 12) or saline (n = 12) infusion for 13 weeks. At the end of treatment, HC/A was repeated, and the remnant pancreas (head-body) was harvested. Insulin sensitivity increased dramatically after exenatide treatment and was accompanied by a decrease in insulin and C-peptide secretion, while the insulin secretion/insulin resistance (disposition) index increased by about 2-fold. β, α, and δ cell relative volumes in exenatide-treated baboons were significantly increased compared with saline-treated controls, primarily as the result of increased islet cell replication. Features of cellular stress and secretory dysfunction were present in islets of saline-treated baboons and absent in islets of exenatide-treated baboons. In conclusion, chronic administration of exenatide exerts proliferative and cytoprotective effects on β, α, and δ cells and produces a robust increase in insulin sensitivity in nonhuman primates.
Mots-clé
Animals, Apoptosis/drug effects, Blood Glucose/analysis, Cell Proliferation/drug effects, Cell Transdifferentiation/drug effects, Diabetes Mellitus, Type 2/blood, Diabetes Mellitus, Type 2/drug therapy, Diabetes Mellitus, Type 2/pathology, Disease Models, Animal, Exenatide/pharmacology, Exenatide/therapeutic use, Female, Glucose Clamp Technique, Humans, Hypoglycemic Agents/pharmacology, Hypoglycemic Agents/therapeutic use, Infusions, Intravenous, Insulin/metabolism, Insulin Resistance, Islets of Langerhans/drug effects, Islets of Langerhans/pathology, Male, Papio, B cells, Endocrinology, Glucose metabolism, Insulin signaling
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/11/2019 10:53
Dernière modification de la notice
25/02/2021 8:09