Glucagon-like peptide-1 (GLP-1) is a member of a large family of incretin hormones secreted in nutrient-dependent response.GLP-1 acts on GLP-1 receptor (GLP-1R) that is highly expressed on pancreatic β-cells.The peptide is very promising for development of diabetes treatment and diagnosis.However,the pharmaceutical effects of the peptide suffer from in vivo instability and short life due to degradation by Dipeptidylpeptidase-1 (DPP-4).We have integrated the 30 amino acid peptide GLP-1 into a stable host protein by rational design.The de novo designed protein bound to GLP-1R as demonstrated by immunostaining analyses of GLP-1R expressing cells.In vitro tests with a rat insulinoma β-cell line RINm5F indicated that the designed protein had strong activity of stimulating oroduction of intracellular cAMP (the activity is comparable to that of native peptide GLP-1 and exendin-4).