Structural requirements for biological activity of glucagon‐like peptide‐I

Glucagon‐like peptide‐I (GLP‐I) is encoded together with glucagon by the glucagon gene and is related in its structure to the glucagon‐secretin family of peptides. Three of the predicted forms of the peptide, a 37‐residue long GLP‐I(1–37), a 31‐residue GLP‐I(7–37) and a 30‐residue GLP‐I(7–36) amide as well as three analogs des [Gly 37 , Arg 36 ] GLP‐I(7–37), des [Gly 37 , Arg 36 , Gly 35 ] GLP‐I(7–37) and des [His 7 ] GLP‐I(7–37) were synthesized by the stepwise solid phase method. These synthetic peptides were used to define the structural domains required for the binding of GLP‐I to the pancreatic beta cell. The competitive binding experiments showed that both the amino and carboxyl terminal domains of the molecule contribute to GLP‐I binding. In these experiments glucagon, another peptide that stimulates insulin secretion, was a weak full agonist of GLP‐I binding. Results from these studies provide further characterization of the physiological role of this new peptide.