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 - 2016/5
Y1 - 2016/5
N2 - Peptide YY (PYY) is a 36-amino-acid peptide released from enteroendocrine cells upon food intake. The NH2 terminally truncated metabolite, PYY3–36, exerts anorexic effects and has received considerable attention as a possible antiobesity drug target. The kinetics and degradation products of PYY metabolism are not well described. A related peptide, neuropeptide Y, may be degraded from the COOH terminus, and in vivo studies in pigs revealed significant COOH-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 eight 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 coadministration of sitagliptin was eliminated with half-lives of 10.1 ± 0.5 and 9.4 ± 0.8 min (means ± SE) and metabolic clearance rates of 15.7 ± 1.5 and 14.1 ± 1.1 ml·kg−1·min−1 after infusion, whereas PYY3–36 was eliminated with a significantly longer half-life of 14.9 ± 1.3 min and a metabolic clearance rate of 9.4 ± 0.6 ml·kg−1·min−1. We conclude that, upon intravenous infusion in healthy men, PYY is inactivated by cleavage of the two COOHterminal amino acids. In healthy men, 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 NH2 terminally truncated metabolite, PYY3–36, exerts anorexic effects and has received considerable attention as a possible antiobesity drug target. The kinetics and degradation products of PYY metabolism are not well described. A related peptide, neuropeptide Y, may be degraded from the COOH terminus, and in vivo studies in pigs revealed significant COOH-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 eight 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 coadministration of sitagliptin was eliminated with half-lives of 10.1 ± 0.5 and 9.4 ± 0.8 min (means ± SE) and metabolic clearance rates of 15.7 ± 1.5 and 14.1 ± 1.1 ml·kg−1·min−1 after infusion, whereas PYY3–36 was eliminated with a significantly longer half-life of 14.9 ± 1.3 min and a metabolic clearance rate of 9.4 ± 0.6 ml·kg−1·min−1. We conclude that, upon intravenous infusion in healthy men, PYY is inactivated by cleavage of the two COOHterminal amino acids. In healthy men, 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
SN - 1522-1490
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)
IS - 1
ER -
