Exenatide regulates pancreatic islet integrity and insulin sensitivity in the nonhuman primate baboon Papio hamadryas.

Details

Serval ID
serval:BIB_893519A0D48A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Exenatide regulates pancreatic islet integrity and insulin sensitivity in the nonhuman primate baboon Papio hamadryas.
Journal
JCI insight
Author(s)
Fiorentino T.V., Casiraghi F., Davalli A.M., Finzi G., La Rosa S., Higgins P.B., Abrahamian G.A., Marando A., Sessa F., Perego C., Guardado-Mendoza R., Kamath S., Ricotti A., Fiorina P., Daniele G., Paez A.M., Andreozzi F., Bastarrachea R.A., Comuzzie A.G., Gastaldelli A., Chavez A.O., Di Cairano E.S., Frost P., Luzi L., Dick E.J., Halff G.A., DeFronzo R.A., Folli F.
ISSN
2379-3708 (Electronic)
ISSN-L
2379-3708
Publication state
Published
Issued date
17/10/2019
Peer-reviewed
Oui
Volume
4
Number
20
Pages
e93091
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
11/11/2019 9:53
Last modification date
01/11/2020 6:23
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