Effects of cholecystokinin on appetite and pyloric motility during physiological hyperglycemia

Recent studies suggest that the interaction between small intestinal nutrie nt stimulation and the blood glucose concentration is important in the regu lation of gastric motility and appetite. The purpose of this study was to d etermine whether the effects of cholecystokinin octapeptide (CCK-8) on antr opyloric motility and appetite are influenced by changes in the blood gluco se concentration within the normal postprandial range. Seven healthy volunt eers were studied on 4 separate days. A catheter incorporating a sleeve sen sor was positioned across the pylorus, and the blood glucose was stabilized at either 4 mmol/l (2 days) or 8 mmol/l (2 days). After the desired blood glucose had been maintained for 90 min, an intravenous infusion of either C CK-8 (2 ng . kg(-1) .(.)min(-1)) or saline (control) was given for 60 min. Thirty minutes after the infusion began, the catheter was removed and subje cts drank 400 mi of water with guar gum before being offered a buffet meal. The amount of food consumed (kcal) was quantified. The order of the studie s was randomized and single-blinded. There were fewer antral waves at a blo od glucose of 8 than at 4 mmol/l during the 90-min period before the infusi ons (P < 0.05) and during the first 30 min of CCK-8 or saline infusion (P = 0.07). CCK-8 suppressed antral waves (P < 0.05), stimulated isolated pylor ic pressure waves (IPPWs) (P < 0.01), and increased basal pyloric pressure (P < 0.005) compared with control. During administration of CCK-8, basal py loric pressure (P < 0.01), but not the number of IPPWs, was greater at a bl ood glucose of 8 mmol/l than at 4 mmol/l. CCK-8 suppressed the energy intak e at the buffet meal (P < 0.01), with no significant difference between the two blood glucose concentrations. We conclude that the acute effect of exo genous CCK-8 on basal pyloric pressure, but not appetite, is modulated by p hysiological changes in the blood glucose concentration.