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Binding, agonism, internalization, and -arrestin recruitment Studies published by 49 and 48 have documented the physiologic relevance of internalization and -arrestin recruitment in response to specific interactions with both the GLP-1R and Y2-R 49 demonstrated that the extent of internalization and receptor trafficking mediated by Ex-4 (the scaffold upon which GEP44 is built) has a direct impact on the ISR and that efforts to retain GLP-1R on the cell surface result in enhanced and sustained insulin release