title: Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery.
abstract: Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and β-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin-(9-39) (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose-tolerant patients were studied after RYGB in a randomized, placebo-controlled, 4-day crossover study with standard mixed-meal tests and concurrent administration of placebo, oral sitagliptin, Ex-9 infusion, or combined Ex-9-sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated β-cell function, and aggravated postprandial hyperglucagonemia compared with placebo, whereas sitagliptin had no effect despite two- to threefold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or β-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4-sensitive glucose-lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB.
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Maria.Saur.Svane@regionh.dk.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Svane
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Kirstine N
authors.initials: KN
authors.lastname: Bojsen-Møller
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark;
authors.forename: Signe
authors.initials: S
authors.lastname: Nielsen
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Nils B
authors.initials: NB
authors.lastname: Jørgensen
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Carsten
authors.initials: C
authors.lastname: Dirksen
authors.affiliation: Department of Surgical and Medical Gastroenterology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; and.
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
authors.affiliation: Department of Surgical and Medical Gastroenterology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; and.
authors.forename: Viggo B
authors.initials: VB
authors.lastname: Kristiansen
authors.affiliation: NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000378:metabolism*; D018592:Cross-Over Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015390:Gastric Bypass; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005934:Glucagon / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D016014:Linear Models; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000601:surgery*; D010446:Peptide Fragments / Q000494:pharmacology; D019518:Postprandial Period; D016037:Single-Blind Method; D000068900:Sitagliptin Phosphate / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; C083773:exendin (9-39); D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000068900:Sitagliptin Phosphate
keywords: Roux-en-Y gastric bypass; dipeptidyl peptidase-4 inhibition; exendin-(9–39); glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide