Effect of food restriction on plasma cholecystokinin levels and exocrine pancreatic function in rats

The objective of this study was to examine the effects of 10% food restrict ion on body weight, plasma cholecystokinin (CCK) levels, and exocrine pancr eatic function in male Sprague-Dawley rats. A matched group of rats with un restricted access to food served as controls. After ingesting the diets for 32 da, the rats were killed and blood obtained for plasma cholecystokinin, glucose, and insulin determinations. To evaluate pancreatic function, the pancreases were removed, weighed, and digested with collagenase to isolate pancreatic acini, which were incubated with maximal stimulating dose of CCK . The fraction of amylase that was released into the medium was measured. T o explore the role of membrane receptors in exocrine pancreatic secretion, CCK receptor affinity and CCK receptor capacity were determined by radiolig and binding assays in isolated, purified membranes from pancreatic acini. C ompared to the control group, rats with 10% food restriction showed (a) red uced body weight gain, (b) increased pancreatic weight, (c) increased plasm a CCK level, and (d) no significant changes in plasma glucose or insulin le vels. The food-restricted group showed a reduction of pancreatic function, assessed by measuring amylase release in response to maximal CCK stimulatio n; the amylase release was diminished by 35% in the food-restricted group. In isolated acinar cell membranes from food-restricted rats, CCK receptor a ffinity and capacity were reduced by 23% and 16%, respectively, compared to controls. These results indicate that consumption of less food than normal affects pancreatic function by a mechanism that evidently involves CCK rel ease and down-regulation of CCK receptors. The data suggest that CCK plays an important physiological role in the adaptation to eating less food, and thereby to the lowering of body weight in rats and, possibly, in other anim als.