Role of cholecystokinin (CCK)-A receptor for pancreatic growth after weaning: a study in a new rat model without gene expression of the CCK-A receptor.

Abstract

This work extends a recent observation that Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have been established as an animal model of non-insulin-dependent diabetes mellitus, show no expression of the cholecystokinin (CCK)-A receptor gene in the pancreas. The CCK-A receptor is known to be involved in regulating pancreatic exocrine function and growth. We examined the growth of the pancreas in terms of wet weight, enzyme compositions, and protein and DNA contents at 5-6 and 24-25 weeks of age in OLETF rats and control (Long-Evans Tokushima; LETO) rats. The pancreatic wet weight increased significantly with age in both OLETF and LETO rats but was significantly lower in OLETF rats than in LETO rats. The total DNA contents in the whole pancreas (cell numbers) were comparable for both strains and increased significantly with age. However, the ratio of protein content to DNA content (the cell size) significantly increased with age in LETO rats, with no increase in OLETF rats. The changes in chymotrypsin, amylase, and insulin with respect to age were in the same direction in both strains: a decrease or no change in total and/or cellular contents of chymotrypsin and insulin and increases in amylase. These results suggest that the CCK-A receptor plays some role in the increase in cell size associated with normal growth of the pancreas from 5 to 25 weeks of age (after weaning).