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found the exendin-4 Trp-cage does not directly interact with the GLP-1R ECD (Runge et al., 2008), although analysis of photo-crosslinking data using the full length receptor showed that the flexible exendin-4 C-terminus might snake over the top of the ECD and form interactions with Phe80, Tyr101 and Phe103 (Koole et al., 2017)

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This meant no PAM enzyme, and the mice developed signs of GLP-1 resistance too, with blood sugar left unregulated despite elevated levels of GLP-1

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