title: Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, nondiabetic men.
abstract: BACKGROUND
  Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are cleaved by dipeptidyl peptidase-4 (DPP-4); plasma activity of DPP-4 may be increased in obesity. The impact of this increase on incretin hormone secretion and metabolism is not known.
  
  
  OBJECTIVE
  The aim of the study was to assess incretin hormone secretion and degradation in lean and obese nondiabetic subjects.
  
  
  METHODS
  We studied the ingestion of a mixed meal (560 kcal) or oral glucose (2 g/kg) in healthy lean (n = 12; body mass index, 20-25 kg/m(2)) or obese (n = 13; body mass index, 30-35 kg/m(2)) males at a University Clinical Research Unit.
  
  
  METHODS
  We measured the area under the curve of plasma intact (i) and total (t) GIP and GLP-1 after meal ingestion and oral glucose.
  
  
  RESULTS
  Plasma DPP-4 activity was higher in the obese subjects (38.5 +/- 3.0 vs. 26.7 +/- 1.6 mmol/min . microl; P = 0.002). Although GIP secretion (AUC(tGIP)) was not reduced in obese subjects after meal ingestion or oral glucose, AUC(iGIP) was lower in obese subjects (8.5 +/- 0.6 vs. 12.7 +/- 0.9 nmol/liter x 300 min; P < 0.001) after meal ingestion. GLP-1 secretion (AUC(tGLP-1)) was reduced in obese subjects after both meal ingestion (7.3 +/- 0.9 vs. 10.0 +/- 0.6 nmol/liter x 300 min; P = 0.022) and oral glucose (6.6 +/- 0.8 vs. 9.6 +/- 1.1 nmol/liter x 180 min; P = 0.035). iGLP-1 was reduced in parallel to tGLP-1.
  
  
  CONCLUSIONS
  1) Release and degradation of the two incretin hormones show dissociated changes in obesity: GLP-1 but not GIP secretion is lower after meal ingestion and oral glucose, whereas GIP but not GLP-1 metabolism is increased after meal ingestion. 2) Increased plasma DPP-4 activity in obesity is not associated with a generalized augmented incretin hormone metabolism.
authors.affiliation: Department of Clinical Sciences Lund, B11 BMC, SE-2221 84 Lund, Sweden.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carr
authors.forename: Marianne O
authors.initials: MO
authors.lastname: Larsen
authors.forename: Katarina
authors.initials: K
authors.lastname: Jelic
authors.forename: Ola
authors.initials: O
authors.lastname: Lindgren
authors.forename: Jenny
authors.initials: J
authors.lastname: Vikman
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology; D000328:Adult; D019540:Area Under Curve; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology*; D005502:Food; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000378:metabolism*; D013851:Thinness / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000082:Acetaminophen; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D005947:Glucose