title: DPP-4 inhibition increases GIP and decreases GLP-1 incretin effects during intravenous glucose tolerance test in Wistar rats.
abstract: GIP metabolite [GIP (3-42)] and GLP-1 metabolite [GLP-1 (9-36) amide] have been reported to differ with regard to biological actions. Systemic DPP-4 inhibition can therefore reveal different actions of GIP and GLP-1. In catheter wearing Wistar rats, insulinotropic effects of equipotent doses of GIP (2.0 nmol/kg) and GLP-1 (7-36) amide (4.0 nmol/kg) and vehicle were tested in the absence/presence of DPP-4 inhibition. Blood glucose and insulin were frequently sampled. DPP-4 inhibitor was given at -20 min, the incretin at -5 min and the intravenous glucose tolerance test (0.4 g glucose/kg) commenced at 0 min. G-AUC and I-AUC, insulinogenic index and glucose efflux, were calculated from glucose and insulin curves. Systemic DPP-4 inhibition potentiated the acute GIP incretin effects: I-AUC (115±34 vs. 153±39 ng·min/ml), increased the insulinogenic index (0.74±0.24 vs. 0.99±0.26 ng/mmol), and improved glucose efflux (19.8±3.1 vs. 20.5±5.0 min⁻¹). The GLP-1 incretin effects were diminished: I-AUC (124±18 vs. 106±38 ng·min/ml), the insulinogenic index was decreased (0.70±0.18 vs. 0.50±0.19 ng/mmol), and glucose efflux declined (14.9±3.1 vs. 11.1±3.7 min⁻¹). GLP-1 and GIP differ remarkably in their glucoregulatory actions in healthy rats when DPP-4 is inhibited. These previously unrecognized actions of DPP-4 inhibitors could have implications for future use in humans.
authors.affiliation: Institute of Diabetes 'Gerhardt Katsch' Karlsburg, D-17495 Karlsburg, Germany. freyse@diabetes-karlsburg.de
authors.forename: Ernst-Joachim
authors.initials: EJ
authors.lastname: Freyse
authors.forename: Sabine
authors.initials: S
authors.lastname: Berg
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Kohnert
authors.forename: Peter
authors.initials: P
authors.lastname: Heinke
authors.forename: Eckhard
authors.initials: E
authors.lastname: Salzsieder
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D054795:Incretins / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D007532:Isoleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D007328:Insulin; D013844:Thiazoles; C114061:isoleucyl-thiazolidide; D007532:Isoleucine; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4