Selective stimulation of insulin secretion by CCK-4 analogues having N-terminal modifications.

Synthetic analogues of CCK-4 in which Trp was replaced by D-Pro (peptide I), Thz (peptide II) and delta Pro (peptide III) have been studied for their insulin and glucagon releasing activities from the islets of Langerhans in vitro. Peptide I has been found to be the most potent insulin releaser among the three analogues and its activity is comparable to that of CCK-4. Unlike CCK-4, its three analogues (peptides I-III) do not stimulate the release of glucagon with basal concentration of glucose in the medium. However, with increasing glucose concentration, all the three analogues potentiate the glucose stimulus for insulin release.