@article{fang_influence_2020, title = {The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists}, copyright = {© 2020, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NonCommercial-NoDerivs 4.0 International), CC BY-NC-ND 4.0, as described at http://creativecommons.org/licenses/by-nc-nd/4.0/}, url = {https://www.biorxiv.org/content/10.1101/2020.02.24.961524v1}, doi = {10.1101/2020.02.24.961524}, abstract = {{\textless}h3{\textgreater}Abstract{\textless}/h3{\textgreater} {\textless}p{\textgreater}Signal bias and membrane trafficking have recently emerged as important considerations in the therapeutic targeting of the glucagon-like peptide-1 receptor (GLP-1R) in type 2 diabetes and obesity. In the present study, we have evaluated a peptide series with varying sequence homology between native GLP-1 and exendin-4, the archetypal ligands on which approved GLP-1R agonists are based. We find notable differences in agonist-mediated signalling, endocytosis and recycling, dependent both on the introduction of a His → Phe switch at position 1 and the specific mid-peptide helical regions and C-termini of the two agonists. These observations were linked to insulin secretion in a beta cell model and provide insights into how ligand factors influence GLP-1R function at the cellular level.{\textless}/p{\textgreater}{\textless}h3{\textgreater}Graphical abstract{\textless}/h3{\textgreater}}, language = {en}, urldate = {2020-03-31}, journal = {bioRxiv}, author = {Fang, Zijian and Chen, Shiqian and Pickford, Philip and Broichhagen, Johannes and Hodson, David J. and Corrêa, Ivan R. and Kumar, Sunil and Görlitz, Frederik and Dunsby, Christopher and French, Paul and Rutter, Guy A. and Tan, Tricia and Bloom, Stephen R. and Tomas, Alejandra and Jones, Ben}, month = feb, year = {2020}, note = {Publisher: Cold Spring Harbor Laboratory Section: New Results}, keywords = {WP4}, pages = {2020.02.24.961524}, }