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Furthermore, when EX4 was co-expressed as a membrane-tethered protein, deletion of its first three residues had little effect on activation of the full-length GLP-1R, suggesting that the membrane-tethered expression could effectively increase the local concentrations of the fusion proteins (Figure 7c), which further supports that the N-terminal residues of EX4 are not required for activation of GLP-1R

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29 In terms of the nervous system, GLP-1 receptor (GLP-1R) expression is enriched in central nervous system (CNS) regions, including the hypothalamus, which regulates appetite, and the brainstem, which primarily secretes brain-derived GLP-1, as well as in the peripheral vagus nerve