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- W3007972005 abstract "Abstract 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. Graphical abstract" @default.
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- W3007972005 date "2020-02-25" @default.
- W3007972005 modified "2023-10-09" @default.
- W3007972005 title "The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists" @default.
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- W3007972005 doi "https://doi.org/10.1101/2020.02.24.961524" @default.
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