Cholecystokinin (CCK)‐33 Stimulates Insulin Secretion from the Perfused Rat Pancreas: Studies on the Structure‐Activity Relationship

Abstract

Cholecystokinin (CCK)-33 is known to stimulate insulin secretion. Presently, using the perfused rat pancreas, we have characterized the active site in the CCK-33 molecule that is responsible for this effect by the use of different CCK fragments. We found that CCK-33, CCK-8 and CCK-7 (1 nM) all significantly stimulated insulin secretion in the presence of 4.4 mM or 6.7 mM glucose. However, CCK-7 was much less potent than the longer forms. In contrast, CCK-4, CCK-6 and CCK-33 (1-21) had no effect on insulin secretion. We conclude that the shortest CCK-form that stimulates insulin secretion at 1 nM is the C-terminal heptapeptide CCK-7. However, CCK-8 is much more potent than CCK-7 in this respect.