In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans

Research output: Contribution to journalJournal articlepeer-review

Standard

In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans. / Toräng, Signe; Bojsen-Møller, Kirstine N; Svane, Maria S; Hartmann, Bolette; Rosenkilde, Mette Marie; Madsbad, Sten; Holst, Jens Juul.

In: A J P: Regulatory, Integrative and Comparative Physiology (Online), Vol. 310, No. 1, 27.01.2016, p. R866-R874.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Toräng, S, Bojsen-Møller, KN, Svane, MS, Hartmann, B, Rosenkilde, MM, Madsbad, S & Holst, JJ 2016, 'In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans', A J P: Regulatory, Integrative and Comparative Physiology (Online), vol. 310, no. 1, pp. R866-R874. https://doi.org/10.1152/ajpregu.00394.2015

APA

Toräng, S., Bojsen-Møller, K. N., Svane, M. S., Hartmann, B., Rosenkilde, M. M., Madsbad, S., & Holst, J. J. (2016). In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans. A J P: Regulatory, Integrative and Comparative Physiology (Online), 310(1), R866-R874. https://doi.org/10.1152/ajpregu.00394.2015

Vancouver

Toräng S, Bojsen-Møller KN, Svane MS, Hartmann B, Rosenkilde MM, Madsbad S et al. In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans. A J P: Regulatory, Integrative and Comparative Physiology (Online). 2016 Jan 27;310(1):R866-R874. https://doi.org/10.1152/ajpregu.00394.2015

Author

Toräng, Signe ; Bojsen-Møller, Kirstine N ; Svane, Maria S ; Hartmann, Bolette ; Rosenkilde, Mette Marie ; Madsbad, Sten ; Holst, Jens Juul. / In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans. In: A J P: Regulatory, Integrative and Comparative Physiology (Online). 2016 ; Vol. 310, No. 1. pp. R866-R874.

Bibtex

@article{0609d7501c33434bb2adf179643f6da1,
title = "In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans",
abstract = "Peptide YY (PYY) is a 36 amino acid peptide released from enteroendocrine cells upon food intake. The N-terminally truncated metabolite, PYY3-36 exerts anorexic effects and has received considerable attention as a possible anti-obesity drug target. The kinetics and degradation products of PYY metabolism are not well described. A related peptide, Neuropeptide Y, may be degraded from the C-terminus, and in vivo studies in pigs revealed significant C-terminal degradation of PYY. We therefore investigated PYY metabolism in vitro after incubation in human blood and plasma and in vivo after infusion of PYY1-36 and PYY3-36 in 8 young, healthy men. A metabolite, corresponding to PYY3-34, was formed after incubation in plasma and blood and during the infusion of PYY. PYY3-34 exhibited no agonistic or antagonistic effects on the Y2 receptor. PYY1-36 infused with and without co-administration of sitagliptin was eliminated with half-lives of 10.1 ± 0.5 and 9.4 ± 0.8 min (mean±SEM) and metabolic clearance rates of 15.7 ± 1.5 and 14.1 ± 1.1 mL/kg•min after infusion, whereas PYY3-36 was eliminated with a significantly longer half-life of 14.9 ± 1.3 minutes and a metabolic clearance rate of 9.4± 0.6 mL/kg•minutes . We conclude that upon intravenous infusion in healthy males, PYY is inactivated by cleavage of the two C-terminal amino acids. In healthy males, PYY3-36 has a longer half-life than PYY1-36.",
author = "Signe Tor{\"a}ng and Bojsen-M{\o}ller, {Kirstine N} and Svane, {Maria S} and Bolette Hartmann and Rosenkilde, {Mette Marie} and Sten Madsbad and Holst, {Jens Juul}",
note = "Copyright {\textcopyright} 2015, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.",
year = "2016",
month = jan,
day = "27",
doi = "10.1152/ajpregu.00394.2015",
language = "English",
volume = "310",
pages = "R866--R874",
journal = "A J P: Regulatory, Integrative and Comparative Physiology (Online)",
issn = "1522-1490",
publisher = "American Physiological Society",
number = "1",

}

RIS

TY - JOUR

T1 - In vivo and in vitro degradation of peptide YY3-36 to inactive peptide YY3-34 in humans

AU - Toräng, Signe

AU - Bojsen-Møller, Kirstine N

AU - Svane, Maria S

AU - Hartmann, Bolette

AU - Rosenkilde, Mette Marie

AU - Madsbad, Sten

AU - Holst, Jens Juul

N1 - Copyright © 2015, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.

PY - 2016/1/27

Y1 - 2016/1/27

N2 - Peptide YY (PYY) is a 36 amino acid peptide released from enteroendocrine cells upon food intake. The N-terminally truncated metabolite, PYY3-36 exerts anorexic effects and has received considerable attention as a possible anti-obesity drug target. The kinetics and degradation products of PYY metabolism are not well described. A related peptide, Neuropeptide Y, may be degraded from the C-terminus, and in vivo studies in pigs revealed significant C-terminal degradation of PYY. We therefore investigated PYY metabolism in vitro after incubation in human blood and plasma and in vivo after infusion of PYY1-36 and PYY3-36 in 8 young, healthy men. A metabolite, corresponding to PYY3-34, was formed after incubation in plasma and blood and during the infusion of PYY. PYY3-34 exhibited no agonistic or antagonistic effects on the Y2 receptor. PYY1-36 infused with and without co-administration of sitagliptin was eliminated with half-lives of 10.1 ± 0.5 and 9.4 ± 0.8 min (mean±SEM) and metabolic clearance rates of 15.7 ± 1.5 and 14.1 ± 1.1 mL/kg•min after infusion, whereas PYY3-36 was eliminated with a significantly longer half-life of 14.9 ± 1.3 minutes and a metabolic clearance rate of 9.4± 0.6 mL/kg•minutes . We conclude that upon intravenous infusion in healthy males, PYY is inactivated by cleavage of the two C-terminal amino acids. In healthy males, PYY3-36 has a longer half-life than PYY1-36.

AB - Peptide YY (PYY) is a 36 amino acid peptide released from enteroendocrine cells upon food intake. The N-terminally truncated metabolite, PYY3-36 exerts anorexic effects and has received considerable attention as a possible anti-obesity drug target. The kinetics and degradation products of PYY metabolism are not well described. A related peptide, Neuropeptide Y, may be degraded from the C-terminus, and in vivo studies in pigs revealed significant C-terminal degradation of PYY. We therefore investigated PYY metabolism in vitro after incubation in human blood and plasma and in vivo after infusion of PYY1-36 and PYY3-36 in 8 young, healthy men. A metabolite, corresponding to PYY3-34, was formed after incubation in plasma and blood and during the infusion of PYY. PYY3-34 exhibited no agonistic or antagonistic effects on the Y2 receptor. PYY1-36 infused with and without co-administration of sitagliptin was eliminated with half-lives of 10.1 ± 0.5 and 9.4 ± 0.8 min (mean±SEM) and metabolic clearance rates of 15.7 ± 1.5 and 14.1 ± 1.1 mL/kg•min after infusion, whereas PYY3-36 was eliminated with a significantly longer half-life of 14.9 ± 1.3 minutes and a metabolic clearance rate of 9.4± 0.6 mL/kg•minutes . We conclude that upon intravenous infusion in healthy males, PYY is inactivated by cleavage of the two C-terminal amino acids. In healthy males, PYY3-36 has a longer half-life than PYY1-36.

U2 - 10.1152/ajpregu.00394.2015

DO - 10.1152/ajpregu.00394.2015

M3 - Journal article

C2 - 26818056

VL - 310

SP - R866-R874

JO - A J P: Regulatory, Integrative and Comparative Physiology (Online)

JF - A J P: Regulatory, Integrative and Comparative Physiology (Online)

SN - 1522-1490

IS - 1

ER -

ID: 160636620