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 restriction on body weight, plasma cholecystokinin (CCK) levels, and exocrine pancreatic function in male Sprague-Dawley rats. A matched group of rats with unrestricted 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. To explore the role of membrane receptors in exocrine pancreatic secretion, CCK receptor affinity and CCK receptor capacity were determined by radioligand binding assays in isolated, purified membranes from pancreatic acini. Compared to the control group, rats with 10% food restriction showed (a) reduced body weight gain, (b) increased pancreatic weight, (c) increased plasma CCK level, and (d) no significant changes in plasma glucose or insulin levels. The food-restricted group showed a reduction of pancreatic function, assessed by measuring amylase release in response to maximal CCK stimulation; the amylase release was diminished by 35% in the food-restricted group. In isolated acinar cell membranes from food-restricted rats, CCK receptor affinity 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 release and downregulation 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 animals.