Zander_2006_Diabetologia_49_369

Reference

Title : The metabolite generated by dipeptidyl-peptidase 4 metabolism of glucagon-like peptide-1 has no influence on plasma glucose levels in patients with type 2 diabetes - Zander_2006_Diabetologia_49_369
Author(s) : Zander M , Madsbad S , Deacon CF , Holst JJ
Ref : Diabetologia , 49 :369 , 2006
Abstract :

AIM/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) is metabolised by the enzyme dipeptidyl-peptidase 4 (DPP-4), generating a metabolite with potential antagonistic properties. This study was conducted to evaluate the effect of that metabolite on plasma glucose levels in patients with type 2 diabetes. MATERIALS AND
METHODS: The randomised crossover study consisted of five regimens: (1) i.v. infusion of GLP-1 (1.2 pmol kg(-1) min(-1); IV); (2 and 3) s.c. infusion of GLP-1 (2.4 and 9.6 pmol kg(-1) min(-1); LSC, HSC); (4) s.c. infusion of GLP-1 (2.4 pmol kg(-1) min(-1)) in combination with a DPP-4 inhibitor (IB); and (5) s.c. infusion of saline (154 mmol NaCl/l; SAL). Seven patients with type 2 diabetes participated in all protocols.
RESULTS: Plasma levels of intact GLP-1 increased from 7+/-1 (SAL) to 17+/-3 (LSC), 61+/-7 (IB), 62+/-5 (IV) and 94+/-10 (9.6 s.c.) pmol/l, p<0.0001. Plasma concentrations of the metabolite increased from 1+/-3 (SAL) and 2+/-6 (IB) pmol/l to 42+/-4 (LSC), 64+/-8 (IV) and 327+/-16 (HSC) pmol/l, p<0.0001. Mean plasma glucose levels at 6 h decreased from 12.4+/-1.1 (SAL) mmol/l to 10.4+/-1.1 (LSC), 8.6+/-0.6 (IB), 8.8+/-0.8 (IV) and 9.1+/-0.9 (HSC) mmol/l, p<0.0001. CONCLUSIONS/INTERPRETATION: At approximately similar concentrations of intact GLP-1 (IV, IB, HSC), but with widely ranging metabolite concentrations, the effect on plasma glucose levels was equal, indicating that the presence of the metabolite does not antagonise the glucose-lowering effect of GLP-1.

PubMedSearch : Zander_2006_Diabetologia_49_369
PubMedID: 16385384

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Citations formats

Zander M, Madsbad S, Deacon CF, Holst JJ (2006)
The metabolite generated by dipeptidyl-peptidase 4 metabolism of glucagon-like peptide-1 has no influence on plasma glucose levels in patients with type 2 diabetes
Diabetologia 49 :369

Zander M, Madsbad S, Deacon CF, Holst JJ (2006)
Diabetologia 49 :369