Journal
EBIOMEDICINE
Volume 7, Issue -, Pages 112-120Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2016.03.034
Keywords
Gut hormones; GLP-1; Low-abundant peptides; Mass-spectrometry; Proteomics
Funding
- NNF Center for Basic Metabolic Research [Holst Group] Funding Source: researchfish
- Novo Nordisk Fonden [NNF16OC0020224, NNF15OC0016230, NNF12OC1015904] Funding Source: researchfish
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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 platformis a powerful resource for identifying and characterizing metabolically active low-abundance peptides. (C) 2016 The Authors. Published by Elsevier B.V.
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