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While we could not measure any changes in receptor conformational shift following exendin-4 binding between GLP-1R WT and V229A (Supplementary Figure 2B, C), quantification of GLP-1R plasma membrane diffusion coefficients using RICS in INS-1 832/3 SNAP/FLAG-hGLP-1R WT versus V229A cells revealed a pronounced reduction in GLP-1R V229A plasma membrane diffusion compared to WT GLP-1R under vehicle conditions (Figure 4A, B), to a similar extent to the reduction caused by exendin-4 binding to GLP-1R WT, as observed here and previously (33), and recapitulating the effect triggered by reduced cholesterol levels following simvastatin exposure (Supplementary Figure 1C, D)

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Understanding the Side Effects Like all medications, GLP-1 drugs can cause side effects