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.
|
Authors | Nicolai J Wewer Albrechtsen, Daniel Hornburg, Reidar Albrechtsen, Berit Svendsen, Signe Toräng, Sara L Jepsen, Rune E Kuhre, Marie Hansen, Charlotte Janus, Andrea Floyd, Asger Lund, Tina Vilsbøll, Filip K Knop, Henrik Vestergaard, Carolyn F Deacon, Felix Meissner, Matthias Mann, Jens J Holst, Bolette Hartmann |
Journal | EBioMedicine
(EBioMedicine)
Vol. 7
Pg. 112-20
(May 2016)
ISSN: 2352-3964 [Electronic] Netherlands |
PMID | 27322465
(Publication Type: Journal Article)
|
Copyright | Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Biomarkers
- Oxyntomodulin
- Glucagon-Like Peptide 1
- Dipeptidyl Peptidase 4
|
Topics |
- Animals
- Biomarkers
(blood)
- Diabetes Mellitus, Type 2
(blood)
- Dipeptidyl Peptidase 4
(blood)
- Disease Models, Animal
- Gastric Bypass
- Glucagon-Like Peptide 1
(blood)
- Humans
- Mass Spectrometry
(methods)
- Mice
- Oxyntomodulin
(blood, isolation & purification)
- Proteomics
(methods)
|