Influence of hyperglycemia on the satiating effect of CCK in humans

In the present study the effects of intraduodenal (i.d.) fat (endogenous CCK) and of CCK infusion on satiety were studied during normo-and hyperglycemic conditions. Eight healthy subjects participated in two protocols consisting of two experiments each. First protocol: (a) normoglycemia (control) with i.d. emulsified fat (i.d. fat) infusion, (b) acute hyperglycemia (HG) with plasma glucose levels stabilized at 15 mmol/L and i.d. fat infusion. In the second protocol the effect of exogenous cholecystokinin (CCK) on satiety was studied during normo- and hyperglycemia. Intraduodenal fat (Intralipid 10%) was infused at a dose of 1 g/h via a nasoduodenal tube in the first protocol, whereas in the second protocol CCK-33 was infused intravenously at a dose of 0.5 IDU/kg x h. Satiety was scored using visual analog scales (VAS). Plasma CCK levels were determined at regular intervals. During infusion of i.d. fat and i.v. CCK the VAS scores of wish to eat, hunger, and prospective feeding decreased significantly (p<0.05) in the normoglycemic experiments. During hyperglycemia satiety did not significantly change in the basal period; however, the scores of wish to eat, hunger, and prospective feeding increased significantly (p<0.05) when i.d. fat or i.v. CCK was administered. Plasma CCK levels in the basal and the stimulated period were not significantly different between normo- and hyperglycemia. In summary, the present study shows that in healthy humans volunteers 1) during normoglycemic conditions satiety can be induced by very low dose of i.d. fat and by CCK infusion, 2) during hyperglycemia the effect of i.d. fat and CCK on satiety are reversed, resulting in increased appetite.