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EBioMedicine. 2016 May;7:112-20. doi: 10.1016/j.ebiom.2016.03.034. Epub 2016 Mar 31.

Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma.

Author information

1
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
2
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
3
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
4
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Department of Surgery, Division of Bariatric Surgery, Køge Hospital, University of Copenhagen, Copenhagen, Denmark.
6
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
7
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
8
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
9
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
10
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
11
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: jjholst@sund.ku.dk.

Abstract

Low-abundance regulatory peptides, including metabolically important gut hormones, have shown promising therapeutic potential. Here, we present a streamlined mass spectrometry-based platform for identifying and characterizing low-abundance regulatory peptides in humans. We demonstrate the clinical applicability of this platform by studying a hitherto neglected glucose- and appetite-regulating gut hormone, namely, oxyntomodulin. Our results show that the secretion of oxyntomodulin in patients with type 2 diabetes is significantly impaired, and that its level is increased by more than 10-fold after gastric bypass surgery. Furthermore, we report that oxyntomodulin is co-distributed and co-secreted with the insulin-stimulating and appetite-regulating gut hormone glucagon-like peptide-1 (GLP-1), is inactivated by the same protease (dipeptidyl peptidase-4) as GLP-1 and acts through its receptor. Thus, oxyntomodulin may participate with GLP-1 in the regulation of glucose metabolism and appetite in humans. In conclusion, this mass spectrometry-based platform is a powerful resource for identifying and characterizing metabolically active low-abundance peptides.

KEYWORDS:

GLP-1; Gut hormones; Low-abundant peptides; Mass-spectrometry; Proteomics

PMID:
27322465
PMCID:
PMC4909640
DOI:
10.1016/j.ebiom.2016.03.034
[Indexed for MEDLINE]
Free PMC Article

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