Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, nondiabetic men.
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.
Carr
Richard D
RD
Department of Clinical Sciences Lund, B11 BMC, SE-2221 84 Lund, Sweden.
Larsen
Marianne O
MO
Jelic
Katarina
K
Lindgren
Ola
O
Vikman
Jenny
J
Holst
Jens J
JJ
Deacon
Carolyn F
CF
Ahrén
Bo
B
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
D000082:Acetaminophen; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D005947:Glucose