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

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, vol. 49, no. 2, pp. 369-74. https://doi.org/10.1007/s00125-005-0098-y

APA

Zander, M., Madsbad, S., Deacon, C. F., & Holst, J. J. (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(2), 369-74. https://doi.org/10.1007/s00125-005-0098-y

Vancouver

Zander M, Madsbad S, Deacon CF, Holst JJ. 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. 2006 Feb;49(2):369-74. https://doi.org/10.1007/s00125-005-0098-y

Author

Zander, M ; Madsbad, S ; Deacon, C F ; Holst, Jens Juul. / 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. In: Diabetologia. 2006 ; Vol. 49, No. 2. pp. 369-74.

Bibtex

@article{42f49eed620d4519951ac66aa27be07e,

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",

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.",

keywords = "Blood Glucose, C-Peptide, Cross-Over Studies, Diabetes Mellitus, Type 2, Dipeptidyl Peptidase 4, Enzyme Activation, Enzyme Inhibitors, Female, Glucagon, Glucagon-Like Peptide 1, Humans, Insulin, Male, Middle Aged, Nitriles, Peptides, Pyrrolidines",

author = "M Zander and S Madsbad and Deacon, {C F} and Holst, {Jens Juul}",

year = "2006",

month = feb,

doi = "10.1007/s00125-005-0098-y",

language = "English",

volume = "49",

pages = "369--74",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "2",

}

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