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 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 COOH-terminal amino acids. In healthy men, PYY3-36 has a longer half-life than PYY1-36.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Signe
authors.initials: S
authors.lastname: Toräng
authors.affiliation: NNF Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Endocrinology, Hvidovre Hospital, Kettegårds Allé, Hvidovre, Denmark; and.
authors.forename: Kirstine Nyvold
authors.initials: KN
authors.lastname: Bojsen-Møller
authors.affiliation: NNF Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Endocrinology, Hvidovre Hospital, Kettegårds Allé, Hvidovre, Denmark; and.
authors.forename: Maria Saur
authors.initials: MS
authors.lastname: Svane
authors.affiliation: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mette Marie
authors.initials: MM
authors.lastname: Rosenkilde
authors.affiliation: NNF Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Endocrinology, Hvidovre Hospital, Kettegårds Allé, Hvidovre, Denmark; and.
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; jjholst@sund.ku.dk.
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D019894:Peptide YY / Q000737:chemistry / Q000378:metabolism*; D059748:Proteolysis; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D010446:Peptide Fragments; D019894:Peptide YY
keywords: degradation; kinetics; peptide YY
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