title: The impact of dipeptidyl peptidase 4 inhibition on incretin effect, glucose tolerance, and gastrointestinal-mediated glucose disposal in healthy subjects.
abstract: OBJECTIVE
  Inhibition of dipeptidyl peptidase 4 (DPP4) is thought to intensify the physiological effects of the incretin hormones. We investigated the effects of DPP4 inhibition on plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1), incretin effect, glucose tolerance, gastrointestinal-mediated glucose disposal (GIGD) and gastric emptying in healthy subjects.
  
  
  METHODS
  A randomised, controlled and open-labelled study.
  
  
  METHODS
  Ten healthy subjects (six women; age, 40±5 years (mean±s.e.m.); BMI, 24±3 kg/m(2); fasting plasma glucose, 5.1±0.2 mmol/l and HbA1c, 34±1 mmol/mol (5.3±0.1%)) were randomised to two-paired study days comprising a 4-h 50 g oral glucose tolerance test (OGTT) with paracetamol (A) and an isoglycaemic intravenous (i.v.) glucose infusion (B), with (A1+B1) and without (A2+B2) preceding administration of the DPP4 inhibitor sitagliptin.
  
  
  RESULTS
  Isoglycaemia was obtained in all subjects on the paired study days. Significant increases in fasting levels and OGTT-induced responses of active GLP1 and GIP were seen after DPP4 inhibition. No significant impact of DPP4 inhibition on fasting plasma glucose (5.1±0.1 vs 4.9±0.1 mmol/l, P=0.3), glucose tolerance (area under the curve (AUC) for plasma glucose, 151±35 vs 137±26 mmol/l×min, P=0.7) or peak plasma glucose during OGTT (8.5±0.4 vs 8.1±0.3 mmol/l, P=0.3) was observed. Neither incretin effect (40±9% (without DPP4 inhibitor) vs 40±7% (with DPP4 inhibitor), P=1.0), glucagon responses (1395±165 vs 1223±195 pmol/l×min, P=0.41), GIGD (52±4 vs 56±5%, P=0.40) nor gastric emptying (Tmax for plasma paracetamol: 86±9 vs 80±12 min, P=0.60) changed following DPP4 inhibition.
  
  
  CONCLUSIONS
  These results suggest that acute increases in active incretin hormone levels do not affect glucose tolerance, GIGD, incretin effect, glucagon responses or gastric emptying in healthy subjects.
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkCenter for Diabetes ResearchGentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: N A
authors.initials: NA
authors.lastname: Rhee
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: S H
authors.initials: SH
authors.lastname: Østoft
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: C F
authors.initials: CF
authors.lastname: Deacon
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Center for Diabetes ResearchGentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkCenter for Diabetes ResearchGentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark filipknop@dadlnet.dk.
authors.forename: F K
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods; D006304:Health Status; D006801:Humans; D054795:Incretins / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins