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
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
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, M; Madsbad, S; Deacon, C F; Holst, Jens Juul.
In: Diabetologia, Vol. 49, No. 2, 02.2006, p. 369-74.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - 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
AU - Zander, M
AU - Madsbad, S
AU - Deacon, C F
AU - Holst, Jens Juul
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
KW - Blood Glucose
KW - C-Peptide
KW - Cross-Over Studies
KW - Diabetes Mellitus, Type 2
KW - Dipeptidyl Peptidase 4
KW - Enzyme Activation
KW - Enzyme Inhibitors
KW - Female
KW - Glucagon
KW - Glucagon-Like Peptide 1
KW - Humans
KW - Insulin
KW - Male
KW - Middle Aged
KW - Nitriles
KW - Peptides
KW - Pyrrolidines
U2 - 10.1007/s00125-005-0098-y
DO - 10.1007/s00125-005-0098-y
M3 - Journal article
C2 - 16385384
VL - 49
SP - 369
EP - 374
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 2
ER -
ID: 132053365