CCK-octapeptide injected into cerebral ventricles of sheep decreases plasma insulin level

Cholecystokinin-8 (CCK-8) was injected into the lateral cerebral ventricles (LV) of conscious sheep to determine its effect on secretion of three hormones important in regulation of peripheral metabolism: growth hormone (GH), glucagon, and insulin. Three hr continuous LV injection of 0.64 pmol/min CCK-8 decreased plasma insulin concentration approximately 30% throughout the three hr period, compared to control injection, and this effect occurred independently of whether or not the sheep were permitted to eat during injection. Only high doses of desulfated CCK-8 affected plasma insulin levels, thus suggesting the involvement of specific CCK receptors. Plasma glucose and GH concentrations were unaffected by LV injections, but plasma glucagon concentration was also decreased by CCK-8. LV injection of 0.64 pmol/min CCK-8 in sheep given an IV bolus injection of glucose (1.0 g/kg body mass) resulted in significantly lower plasma insulin and higher plasma glucose concentrations than during control LV injections; thus CCK-8 is capable of suppressing insulin secretion even under stimulated conditions. Since cisterna magna injections of CCK-8 were not effective in suppressing insulin secretion, more rostral brain sites are probably responsible for mediating this effect.