Morphological and biochemical changes in the pancreas of the copper-deficient female rat

Earlier histological studies have demonstrated that copper deficiency results in a selective and progressive atrophy of pancreatic acinar tissue. The present study examined both biochemical and morphological changes of the exocrine pancreas in nutritional copper deficiency. Groups of mature female rats were fed a purified diet either deficient (less than 0.5 micrograms/g) or sufficient (6.2 micrograms/g) in copper for 6 wk. Copper deficiency resulted in distinct ultrastructural changes in acinar cells, including marked variability in zymogen granule content, autophagic vacuoles and dilation of acinar lumen. Pancreatic weight and total DNA, RNA and protein content of the pancreas were similar in both groups of rats, whereas pancreatic amylase, trypsin and chymotrypsin activity was significantly lower in the copper-deficient group. In addition, secretagogue-induced release of these enzymes from dispersed acini isolated from copper-deficient rats was significantly reduced in comparison to enzyme secretion from normal controls. Pancreatic Cu-Zn and Mn superoxide dismutase activity was also found to be significantly lower in the copper-deficient rats than in normal controls. We conclude that nutritional copper deficiency in adult female rats reduces the responsiveness of the pancreas to secretagogues and may increase the susceptibility of the pancreas to oxidative damage.