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

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

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.

MeSH terms

  • 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*
  • Oxyntomodulin / isolation & purification
  • Proteomics / methods*

Substances

  • Biomarkers
  • Oxyntomodulin
  • Glucagon-Like Peptide 1
  • Dipeptidyl Peptidase 4