title: Central GIP signaling stimulates peripheral GIP release and promotes insulin and pancreatic polypeptide secretion in nonhuman primates.
abstract: Glucose-dependent insulinotropic polypeptide (GIP) has important actions on whole body metabolic function. GIP and its receptor are also present in the central nervous system and have been linked to neurotrophic actions. Metabolic effects of central nervous system GIP signaling have not been reported. We investigated whether centrally administered GIP could increase peripheral plasma GIP concentrations and influence the metabolic response to a mixed macronutrient meal in nonhuman primates. An infusion and sampling system was developed to enable continuous intracerebroventricular (ICV) infusions with serial venous sampling in conscious nonhuman primates. Male baboons (Papio sp.) that were healthy and had normal body weights (28.9 ± 2.1 kg) were studied (n = 3). Animals were randomized to receive continuous ICV infusions of GIP (20 pmol·kg-1·h-1) or vehicle before and over the course of a 300-min mixed meal test (15 kcal/kg, 1.5g glucose/kg) on two occasions. A significant increase in plasma GIP concentration was observed under ICV GIP infusion (66.5 ± 8.0 vs. 680.6 ± 412.8 pg/ml, P = 0.04) before administration of the mixed meal. Increases in postprandial, but not fasted, insulin (P = 0.01) and pancreatic polypeptide (P = 0.04) were also observed under ICV GIP. Effects of ICV GIP on fasted or postprandial glucagon, glucose, triglyceride, and free fatty acids were not observed. Our data demonstrate that central GIP signaling can promote increased plasma GIP concentrations independent of nutrient stimulation and increase insulin and pancreatic polypeptide responses to a mixed meal.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas; Southwest National Primate Research Center, San Antonio, Texas; paulb.higgins@gmail.com.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Higgins
authors.affiliation: Southwest National Primate Research Center, San Antonio, Texas.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Shade
authors.affiliation: Department of Genetics, School of Medicine, Autonomous University of Nuevo León (Universidad Autonoma de Nuevo León), Monterrey, Nuevo León, Mexico.
authors.forename: Irám P
authors.initials: IP
authors.lastname: Rodríguez-Sánchez
authors.affiliation: Southwest National Primate Research Center, San Antonio, Texas.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Garcia-Forey
authors.affiliation: Laboratory of Nutrigenetics and Nutrigenomics, National Institute of Genomic Medicine (Instituto Nacional de Medicina Genómica), Mexico City, Mexico.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Tejero
authors.affiliation: Department of Nutrition and UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina.
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas; Southwest National Primate Research Center, San Antonio, Texas.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.affiliation: Southwest National Primate Research Center, San Antonio, Texas; Diabetes Division, Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas; Department of Medicine, Obesity and Comorbidities Research Center, University of Campinas, Campinas, São Paulo, Brazil; and Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Folli
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000378:metabolism*; D057967:Infusions, Intraventricular; D007328:Insulin / Q000378:metabolism*; D008297:Male; D010191:Pancreatic Polypeptide / Q000378:metabolism*; D050418:Pancreatic Polypeptide-Secreting Cells / Q000187:drug effects*; D010215:Papio / Q000378:metabolism*; D019518:Postprandial Period / Q000187:drug effects; D013045:Species Specificity; D013238:Stereotaxic Techniques
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D010191:Pancreatic Polypeptide
keywords: brain; glucose-dependent insulinotropic polypeptide; intracerebroventricular; nonhuman primate