title: Pancreatic polypeptide responses to isoglycemic oral and intravenous glucose in humans with and without intact vagal innervation.
abstract: Secretion of pancreatic polypeptide (PP) from the pancreatic PP cells is controlled partly by vagal mechanisms. Release is stimulated by cephalic stimulation and enteral but not parenteral nutrients. Ambient glucose levels modulate circulating PP levels as hypoglycemia stimulates while hyperglycemia inhibits secretion. The glucose sensing mechanism has yet to be determined but may involve a vagal pathway. To investigate the role of enteral stimuli with or without intact vagal innervation, while controlling for the glucose excursion caused by the OGTT, we measured PP plasma levels by an in-house radioimmunoassay in truncally vagotomized (n=15) and control individuals (n=10). All participants were studied by a 50-g oral glucose tolerance test (OGTT) with or without dipeptidyl peptidase 4 (DPP-4) inhibition (DPP-4i) and a subsequent isoglycemic intravenous glucose infusion (IGII). We included measurements from the DPP-4i day to determine the potential effect of DPP-4-cleaved peptides on PP secretion. In both vagotomized and controls, oral glucose elicited PP secretion. In controls, but not in the vagotomized participants, intravenous glucose significantly inhibited PP secretion suggesting a vagal glucose sensing mechanism dependent on intact vagal innervation. DPP-4i did not alter PP secretion in either group.
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Denmark; The NNF Center for Basic Metabolic Research and The Department of Biomedical Sciences, University of Copenhagen, Denmark; Department of Surgical Gastroenterology C, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Veedfald
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Denmark; The NNF Center for Basic Metabolic Research and The Department of Biomedical Sciences, University of Copenhagen, Denmark.
authors.forename: Astrid
authors.initials: A
authors.lastname: Plamboeck
authors.affiliation: The NNF Center for Basic Metabolic Research and The Department of Biomedical Sciences, University of Copenhagen, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Surgical Gastroenterology C, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Lars B
authors.initials: LB
authors.lastname: Svendsen
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Denmark; The NNF Center for Basic Metabolic Research and The Department of Biomedical Sciences, University of Copenhagen, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: The NNF Center for Basic Metabolic Research and The Department of Biomedical Sciences, University of Copenhagen, Denmark. Electronic address: jjholst@sund.ku.dk.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D005260:Female; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000294:innervation* / Q000378:metabolism*; D014628:Vagotomy
chemical_list: D005947:Glucose
keywords: Glucose; Humans; Pancreatic Polypeptide; Vagal nerve; Vagotomy