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.

Integrity and insulin sensitivity in the nonhuman primate baboon Papio hamadryas

Sessa F.;LA ROSA, STEFANO
2019-01-01

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.
2019
B cells; Endocrinology; Glucose metabolism; Insulin signaling
Fiorentino, T. V.; Casiraghi, F.; Davalli, A. M.; Finzi, G.; Rosa, S. L.; 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.; LA ROSA, Stefano
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2096061
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