Effects of Six Cholecystokinin (CCK) Fragments on Insulin Secretion in the Mouse

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Abstract
In a recent study it was demonstrated that the C-terminal octapeptide of cholecystokinin (CCK-26-33; often abbreviated CCK-8) and CCK-39 (= CCK-6-33) potently and with the same efficacy stimulated basal insulin secretion when injected intravenously to mice. In the present study, the effects of four other CCK fragments, CCK-30-33 (= CCK-4), CCK-1-33 (= CCK-33), CCK-1-21 (= CCK-21) and CCK-10-20, on basal and glucose-induced insulin secretion were studied. It was found that CCK-33 stimulated insulin secretion. At a dose level of 4.25 nmol/kg, plasma insulin concentrations were elevated by 58 .+-. 7 .mu.U/ml (P < 0.001). On the contrary, neither CCK-4, nor CCK-21, nor CCK-10-20 displayed any effect on basal insulin secretion, not even at high dose levels. When injecting CCK-8, CCK-33 or CCK-39 at dose levels substimulatory on basal insulin secretion (0.53 nmol/kg), together with glucose, CCK-39 potentiated glucose-induced insulin secretion whereas CCK-8 and CCK-33 were without effects. In contrast, at the higher dose level of 5.3 nmol/kg, CCK-8, CCK-33, and CCK-39 all potentiated glucose-induced insulin secretion. The three other fragments, CCK-4, CCK-21, and CCK-10-20, were all without effects on glucose-induced insulin secretion. In conclusion, the potent stimulatory action on basal insulin secretion in the mouse exerted by various CCK fragments is confined to the C-terminal octapeptide (= CCK-8 or CCK-26-33). Thus neither CCK-4 nor the N-terminal fragments display any effect. Further, the stimulatory CCK-fragments also potentiate glucose-induced insulin secretion; CCK-39 being more potent in this respect than CCK-8 or CCK-33.