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High affinity agonists that remain bound to GLP-1R within the endosomal pathway tend to result in greater lysosomal targeting of the receptor, whereas lower affinity agonists preferentially lead to receptor recycling ( via proteolytic processing of endosomal GLP-1 ( via the neonatal Fc receptor (FcRn) ( Caveats to GLP-1R Trafficking Studies Reported in the Literature It is important to note that many studies investigating GLP-1R trafficking have used immortalised cell lines overexpressing the GLP-1R, typically stimulated with high agonist concentrations that are well above the physiological range and may even exceed the likely peak concentrations of pharmacological GLP-1RAs in vivo

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doi: 10.3389/fimmu.2025.1514422 149 WangRXuJWeiSLiuX

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