Integrity and insulin sensitivity in the nonhuman primate baboon Papio hamadryas

Teresa Vanessa Fiorentino, Francesca Casiraghi, Alberto M. Davalli, Giovanna Finzi, Stefano La Rosa, Paul B. Higgins, Gregory A. Abrahamian, Alessandro Marando, Fausto Sessa, Carla Perego, Rodolfo Guardado-Mendoza, Subhash Kamath, Andrea Ricotti, Paolo Fiorina, Giuseppe Daniele, Ana M. Paez, Francesco Andreozzi, Raul A. Bastarrachea, Anthony G. Comuzzie, Amalia GastaldelliAlberto O. Chavez, Eliana S. Di Cairano, Patrice Frost, Livio Luzi, Edward J. Dick, Glenn A. Halff, Ralph A. DeFronzo, Franco Folli

Research output: Contribution to journalArticle

4 Scopus citations

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 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 cells and produces a robust increase in insulin sensitivity in nonhuman primates.

Original languageEnglish (US)
Article numbere93091
JournalJCI Insight
Volume4
Issue number20
DOIs
StatePublished - Sep 19 2019

ASJC Scopus subject areas

  • Medicine(all)

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