Pancreatic polypeptide responses to isoglycemic oral and intravenous glucose in humans with and without intact vagal innervation

TY - JOUR

T1 - Pancreatic polypeptide responses to isoglycemic oral and intravenous glucose in humans with and without intact vagal innervation

AU - Veedfald, Simon

AU - Plamboeck, Astrid

AU - Hartmann, Bolette

AU - Svendsen, Lars B

AU - Vilsbøll, Tina

AU - Knop, Filip K

AU - Holst, Jens J

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/8/14

Y1 - 2015/8/14

N2 - 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.

AB - 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.

U2 - 10.1016/j.peptides.2015.07.020

DO - 10.1016/j.peptides.2015.07.020

M3 - Journal article

C2 - 26218807

SN - 0196-9781

VL - 71

SP - 229

EP - 231

JO - Peptides

JF - Peptides

ER -