title: Characterisation of oral and i.v. glucose handling in truncally vagotomised subjects with pyloroplasty.
abstract: OBJECTIVE
  Glucagon-like peptide 1 (GLP1) is rapidly inactivated by dipeptidyl peptidase 4 (DPP4), but may interact with vagal neurons at its site of secretion. We investigated the role of vagal innervation for handling of oral and i.v. glucose.
  
  
  METHODS
  Truncally vagotomised subjects (n=16) and matched controls (n=10) underwent 50 g-oral glucose tolerance test (OGTT)±vildagliptin, a DPP4 inhibitor (DPP4i) and isoglycaemic i.v. glucose infusion (IIGI), copying the OGTT without DPP4i.
  
  
  RESULTS
  Isoglycaemia was obtained with 25±2 g glucose in vagotomised subjects and 18±2 g in controls (P<0.03); thus, gastrointestinal-mediated glucose disposal (GIGD) - a measure of glucose handling (100%×(glucoseOGTT-glucoseIIGI/glucoseOGTT)) - was reduced in the vagotomised compared with the control group. Peak intact GLP1 concentrations were higher in the vagotomised group. Gastric emptying was faster in vagotomised subjects after OGTT and was unaffected by DPP4i. The early glucose-dependent insulinotropic polypeptide response was higher in vagotomised subjects. Despite this, the incretin effect was equal in both groups. DPP4i enhanced insulin secretion in controls, but had no effect in the vagotomised subjects. Controls suppressed glucagon concentrations similarly, irrespective of the route of glucose administration, whereas vagotomised subjects showed suppression only during IIGI and exhibited hyperglucagonaemia following OGTT. DPP4i further suppressed glucagon secretion in controls and tended to normalise glucagon responses in vagotomised subjects.
  
  
  CONCLUSIONS
  GIGD is diminished, but the incretin effect is unaffected in vagotomised subjects despite higher GLP1 levels. This, together with the small effect of DPP4i, is compatible with the notion that part of the physiological effects of GLP1 involves vagal transmission.
authors.affiliation: Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. astridp@sund.ku.dk
authors.forename: Astrid
authors.initials: A
authors.lastname: Plamboeck
authors.forename: Simon
authors.initials: S
authors.lastname: Veedfald
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.forename: André
authors.initials: A
authors.lastname: Wettergren
authors.forename: Lars B
authors.initials: LB
authors.lastname: Svendsen
authors.forename: Søren
authors.initials: S
authors.lastname: Meisner
authors.forename: Claus
authors.initials: C
authors.lastname: Hovendal
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage; D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000368:Aged; D019540:Area Under Curve; D016022:Case-Control Studies; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004381:Duodenal Ulcer / Q000601:surgery; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D008297:Male; D009570:Nitriles / Q000008:administration & dosage*; D011708:Pylorus / Q000601:surgery*; D011759:Pyrrolidines / Q000008:administration & dosage*; D015167:Vagotomy, Truncal / Q000379:methods*; D000077597:Vildagliptin
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D000082:Acetaminophen; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077597:Vildagliptin; D005947:Glucose; D000218:Adamantane