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- W3012148265 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 cyclic AMP signaling, recruitment of β-arrestins, endocytosis, and recycling, dependent both on the introduction of a His → Phe switch at position 1 and the specific midpeptide 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." @default.
- W3012148265 created "2020-03-23" @default.
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- W3012148265 date "2020-03-17" @default.
- W3012148265 modified "2023-10-14" @default.
- W3012148265 title "The Influence of Peptide Context on Signaling and Trafficking of Glucagon-like Peptide-1 Receptor Biased Agonists" @default.
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- W3012148265 doi "https://doi.org/10.1021/acsptsci.0c00022" @default.
- W3012148265 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7155199" @default.
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