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

TY - JOUR

T1 - Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma

AU - Wewer Albrechtsen, Nicolai J

AU - Hornburg, Daniel

AU - Albrechtsen, Reidar

AU - Svendsen, Berit

AU - Toräng, Signe

AU - Jepsen, Sara L

AU - Kuhre, Rune E

AU - Hansen, Marie

AU - Janus, Charlotte

AU - Floyd, Andrea

AU - Lund, Asger

AU - Lauritsen, Tina Vilsbøll

AU - Knop, Filip K

AU - Vestergaard, Henrik

AU - Deacon, Carolyn F

AU - Meissner, Felix

AU - Mann, Matthias

AU - Holst, Jens J

AU - Hartmann, Bolette

N1 - Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.ebiom.2016.03.034

DO - 10.1016/j.ebiom.2016.03.034

M3 - Journal article

C2 - 27322465

SN - 2352-3964

VL - 7

SP - 112

EP - 120

JO - EBioMedicine

JF - EBioMedicine

ER -