Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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 Lauritsen, Filip K Knop, Henrik Vestergaard, Carolyn F Deacon, Felix Meissner, Matthias Mann, Jens J Holst, Bolette Hartmann
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.
|Status||Udgivet - maj 2016|