Intracisternal insulin alters sensitivity to CCK-induced meal suppression in baboons

We have previously reported that intravenous administration of the octapeptide of cholecystokinin (CCK-8) is more effective in reducing single meal size in baboons at noontime than in the morning. We have also reported that immunoreactive insulin levels in the cerebrospinal fluid (CSF) are elevated after animals have recently eaten. To test whether elevated CSF insulin levels can alter the efficacy of intravenous CCK to reduce meal size we administered subthreshold doses of CCK-8 to baboons infused with either synthetic CSF or CSF and insulin (100 microU X kg-1 X day-1) via the cisterna magna. Intravenous CCK-8 alone reduced 30-min meal size from 504 +/- 121 to 378 +/- 113 kcal (n = 7, P = NS). Chronic intracisternal insulin infusion enhanced CCK-8's suppressive effects such that 30-min meal size was reduced from 544 +/- 74 to 240 +/- 108 kcal (n = 7, P less than 0.005). Intracisternal insulin infusion had no significant effect on total food intake, basal plasma insulin and glucose levels, or postprandial plasma insulin and glucose levels. These findings suggest that central insulin may contribute to food intake regulation by modulating the ability of brain-gut peptides to alter single meal size.