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Cardiovasc Diabetol 19(1):156 International Diabetes Federation (2022) Brussels: International Diabetes Federation

Genetic Predisposition Insights and Peptide Pathway Context GLP-1 response varies significantly between individuals

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In line with strong and stable interactions of His1-Ala2 of GLP-1 compared with transient interactions of His1-Gly2 in exendin-4, truncation of these two N-terminal residues reduces GLP-1 affinity by 100-300 fold, whereas for exendin-4, this has no effect, albeit for both peptides, these residues are required for GLP-1R-mediated cAMP production 2225