PuSH - Publication Server of Helmholtz Zentrum München

Jin, S.* ; Wu, W.* ; Liu, S.* ; Wang, Y.* ; Huang, Q.* ; He, K.* ; Ni, Y.* ; Chen, K.* ; Huang, J.* ; Liu, L.* ; Dai, J.* ; Zhan, C.* ; Wang, X.* ; Guan, Y.* ; Blüher, M.

Secreted EMC10 inhibits muscle GLUT4 activity and glucose uptake in mice.

J. Biol. Chem. 301:110296 (2025)
Publ. Version/Full Text Research data DOI PMC
Creative Commons Lizenzvertrag
Open Access Green as soon as Postprint is submitted to ZB.
Manipulation of glucose uptake plays a critical role in muscle glucose disposal. We have shown that the secreted isoform of endoplasmic reticulum membrane protein complex subunit 10 (scEMC10) impairs glucose tolerance in mice and serum scEMC10 is positively associated with insulin resistance and hyperglycemia in humans. In this study, we attempt to investigate whether modulation of muscle glucose uptake implicates in the scEMC10-impacted glucose homeostasis. In mouse models, Emc10 gene knockout elevated, while recombinant scEMC10 treatment reduced, muscle glucose uptake and GLUT4 expression. In myoblasts, scEMC10 inhibited both GLUT4 expression and membrane translocation, and downregulated expression of genes associated with intracellular glucose metabolism. Mechanistically, scEMC10 suppressed the activation of muscle AMPK and insulin signaling cascades. Inhibition of scEMC10 via a neutralizing antibody enhanced muscle glucose uptake in mice, in parallel with heightened GLUT4 expression and membrane translocation, which accounts for an improved whole-body glucose homeostasis. In conclusion, this work identifies scEMC10 as a novel suppressor of muscle glucose uptake, and suggests inhibition of scEMC10 as a therapeutic strategy for type 2 diabetes.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Glut4 ; Glucose Uptake ; Secreted Emc10 ; Skeletal Muscle
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Journal Journal of Biological Chemistry, The
Quellenangaben Volume: 301, Issue: 7, Pages: , Article Number: 110296 Supplement: ,
Publisher American Society for Biochemistry and Molecular Biology
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)