Effect of CCK on insulin, glucagon, and pancreatic polypeptide levels in humans

The present study was designed to determine the effect of low doses of cholecystokinin (CCK) on insulin, glucagon, and pancreatic polypeptide (PP) secretion in the basal state and during prestimulation with amino acids and glucose alone or in combination. Two different amino acid solutions available for use in humans were employed. Aminosteril-N-Hepa was better for the imitation of the so-called "insulinogenic" amino acids while Aminoplasmal L-10 gave more comparable plasma levels of the "glucagonogenic" amino acids as observed after a protein-rich meal. In healthy volunteers, low-dose CCK infusion [Thr28,Nle31-CCK 25-33 (CCK-9)] in stepwise increasing doses of 5, 10, and 20 pmol/kg/h had no effect on basal, glucose-, or amino acid-stimulated insulin release. During the combination of Aminoplasmal + glucose, there was a small and only transient increase of plasma insulin levels that did not occur during Aminosteril + glucose. CCK did not alter glucagon levels either during i.v. amino acids alone or during combination of amino acids with glucose. CCK-stimulated PP levels in the basal state in a dose-dependent manner. This effect was enhanced during i.v. Aminosteril but not i.v. Aminoplasmal infusion. During i.v. glucose, the effect of CCK on PP levels was abolished. In conclusion, the present data demonstrate that CCK is unlikely to be a stimulus of insulin and glucagon secretion in the basal state and also during prestimulation by fairly physiological quantities of amino acid mixtures. On the other hand, the present data support a physiological role of CCK in the regulation of PP secretion.