title: Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes.
abstract: OBJECTIVE
  We sought to determine whether alterations in meal absorption and gastric emptying contribute to the mechanism by which inhibitors of dipeptidyl peptidase-4 (DPP-4) lower postprandial glucose concentrations.
  
  
  METHODS
  We simultaneously measured gastric emptying, meal appearance, endogenous glucose production, and glucose disappearance in 14 subjects with type 2 diabetes treated with either vildaglipitin (50 mg b.i.d.) or placebo for 10 days using a double-blind, placebo-controlled, randomized, crossover design.
  
  
  RESULTS
  Fasting (7.3 +/- 0.5 vs. 7.9 +/- 0.5 mmol/l) and peak postprandial (14.1 +/- 0.6 vs. 15.9 +/- 0.9 mmol/l) glucose concentrations were lower (P < 0.01) after vildagliptin treatment than placebo. Despite lower glucose concentrations, postprandial insulin and C-peptide concentrations did not differ during the two treatments. On the other hand, the integrated (area under the curve) postprandial glucagon concentrations were lower (20.9 +/- 1.6 vs. 23.7 +/- 1.3 mg/ml per 5 h, P < 0.05), and glucagon-like peptide 1 (GLP-1) concentrations were higher (1,878 +/- 270 vs. 1,277 +/- 312 pmol/l per 5 h, P = 0.001) during vildagliptin administration compared with placebo. Gastric emptying and meal appearance did not differ between treatments.
  
  
  CONCLUSIONS
  Vildagliptin does not alter gastric emptying or the rate of entry of ingested glucose into the systemic circulation in humans. DPP-4 inhibitors do not lower postprandial glucose concentrations by altering the rate of nutrient absorption or delivery to systemic circulation. Alterations in islet function, secondary to increased circulating concentrations of active GLP-1, are associated with the decreased postprandial glycemic excursion observed in the presence of vildagliptin.
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. vella.adrian@mayo.edu
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Gerlies
authors.initials: G
authors.lastname: Bock
authors.forename: Paula D
authors.initials: PD
authors.lastname: Giesler
authors.forename: Duane B
authors.initials: DB
authors.lastname: Burton
authors.forename: Denise B
authors.initials: DB
authors.lastname: Serra
authors.forename: Monica Ligueros
authors.initials: ML
authors.lastname: Saylan
authors.forename: Beth E
authors.initials: BE
authors.lastname: Dunning
authors.forename: James E
authors.initials: JE
authors.lastname: Foley
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
mesh_terms: D058892:Adenosine Deaminase Inhibitors; D001066:Appetite; D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004311:Double-Blind Method; D004435:Eating; D005215:Fasting; D005746:Gastric Emptying; D041981:Gastrointestinal Tract / Q000503:physiopathology*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D019518:Postprandial Period
chemical_list: D058892:Adenosine Deaminase Inhibitors; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4