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The clinical manifestations of DN can vary widely, ranging from asymptomatic cases to severe pain and functional impairment

Dynamics of peptide-TMD interactions are correlated with the allosteric effect of G proteins on agonist affinity and G protein conformation The stark contrast in the requirement for stable TMD interactions for exendin-P5 affinity relative to GLP-1, oxyntomodulin and exendin-4, raises important questions regarding molecular mechanisms for peptide binding and receptor activation

Inactive state stabilized by the ECD and ECL1/3 In the GLP-1RFab7F38 structure, the saddle-like ECD loop S116-E127 covers the ECL1 helical region Q211-S219 that partially occupies the orthosteric ECD-binding site (Fig