title: Effects of dipeptidyl peptidase IV inhibition on glycemic, gut hormone, triglyceride, energy expenditure, and energy intake responses to fat in healthy males.
abstract: Fat is the most potent stimulus for glucagon-like peptide-1 (GLP-1) secretion. The aims of this study were to determine whether dipeptidyl peptidase IV (DPP-IV) inhibition would enhance plasma active incretin [glucose-dependent insulinotropic polypeptide (GIP), GLP-1] concentrations and modulate the glycemic, gut hormone, triglyceride, energy expenditure, and energy intake responses to intraduodenal fat infusion. In a double-blind, randomized, placebo-controlled crossover design, 16 healthy lean males received 50 mg vildagliptin (V), or matched placebo (P), before intraduodenal fat infusion (2 kcal/min, 120 min). Blood glucose, plasma insulin, glucagon, active GLP-1, and GIP and peptide YY (PYY)-(3-36) concentrations; resting energy expenditure; and energy intake at a subsequent buffet meal (time = 120-150 min) were quantified. Data are presented as areas under the curve (0-120 min, means ± SE). Vildagliptin decreased glycemia (P: 598 ± 8 vs. V: 573 ± 9 mmol·l⁻¹·min⁻¹, P < 0.05) during intraduodenal lipid. This was associated with increased insulin (P: 15,964 ± 1,193 vs. V: 18,243 ± 1,257 pmol·l⁻¹·min⁻¹, P < 0.05), reduced glucagon (P: 1,008 ± 52 vs. V: 902 ± 46 pmol·l⁻¹·min⁻¹, P < 0.05), enhanced active GLP-1 (P: 294 ± 40 vs. V: 694 ± 78 pmol·l⁻¹·min⁻¹) and GIP (P: 2,748 ± 77 vs. V: 4,256 ± 157 pmol·l⁻¹·min⁻¹), and reduced PYY-(3-36) (P: 9,527 ± 754 vs. V: 4,469 ± 431 pM/min) concentrations compared with placebo (P < 0.05, for all). Vildagliptin increased resting energy expenditure (P: 1,821 ± 54 vs. V: 1,896 ± 65 kcal/day, P < 0.05) without effecting energy intake. Vildagliptin 1) modulates the effects of intraduodenal fat to enhance active GLP-1 and GIP, stimulate insulin, and suppress glucagon, thereby reducing glycemia and 2) increases energy expenditure. These observations suggest that the fat content of a meal, by enhancing GLP-1 and GIP secretion, may contribute to the response to DPP-IV inhibition.
authors.affiliation: University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre for Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and.
authors.forename: Gabriella A
authors.initials: GA
authors.lastname: Heruc
authors.affiliation: University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre for Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.affiliation: University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre for Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and.
authors.forename: Christine
authors.initials: C
authors.lastname: Feinle-Bisset
authors.affiliation: University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre for Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Rayner
authors.affiliation: University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre for Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and.
authors.forename: Natalie
authors.initials: N
authors.lastname: Luscombe-Marsh
authors.affiliation: University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre for Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and tanya.little@adelaide.edu.au.
authors.forename: Tanya J
authors.initials: TJ
authors.lastname: Little
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D001069:Appetite Regulation / Q000187:drug effects; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D002149:Energy Intake / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D018565:Food-Drug Interactions; D005749:Gastric Inhibitory Polypeptide / Q000819:agonists* / Q000097:blood / Q000378:metabolism; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000097:blood / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D019894:Peptide YY / Q000097:blood / Q000378:metabolism; D019518:Postprandial Period; D011759:Pyrrolidines / Q000494:pharmacology; D000077597:Vildagliptin; D055815:Young Adult
chemical_list: D004041:Dietary Fats; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D009570:Nitriles; D010446:Peptide Fragments; D011759:Pyrrolidines; D019894:Peptide YY; C061785:peptide YY (3-36); D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077597:Vildagliptin; D000218:Adamantane
keywords: gastrointestinal hormones; glucose; metabolism