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Discussion In this study, we have identified how single amino acid substitutions to exendin-4 can dramatically enhance insulin secretion via modulation of GLP-1R binding kinetics, biased signaling, and trafficking

MD simulations Initial wild-type GLP-1R model for MD simulations was obtained from the GLP-1R-Fab7F38 structure with modifications: (1) antibody (Fab7F38) and fusion protein (rubredoxin) were removed

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Deactivation Mechanism of Glucagon-like Peptide-1/2 by Dipeptidyl Peptidase 4 Intestinal L-cells and K-cells release the physiologically active forms of GLP-1 and GIP, known as active GLP-1 amide and GIP, in response to oral glucose via increased cAMP (69)

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