Morphological and biochemical changes in the pancreas of copper-deficient rats.

Two types of experimental chronic pancreatic damage were induced in rats by a copper-deficient diet containing D-penicillamine (DP rats) and by a similar diet without D-penicillamine (D rats). At 5-6 weeks after commencement of treatment, serum copper levels showed a significant decrease in both DP rats (1.5 +/- 0.9 micrograms/dl, M +/- SE) and D rats (18.8 +/- 1.4 micrograms/dl) compared with the findings in control rats (111.8 +/- 4.4 micrograms/dl). Histology revealed loss and atrophy of acinar cells in DP rats and mild vacuolar degeneration of acinar cells in D rats, whereas the islets of Langerhans were intact in both groups. The secretion of the exocrine pancreas showed a marked decrease in enzymes and protein output in DP and D rats compared with findings in the control rats. Our study confirmed the relationships between serum copper levels and morphological damage of pancreatic acinar cells or the reduction of enzyme secretion. On the other hand, the reductions in volume and bicarbonate output of pancreatic juice in DP rats and in D rats were detected, but no relationship was found between these reductions and the serum copper levels. The endocrine pancreatic function in DP rats showed a slight disturbance in intravenous glucose tolerance test. These results support the conclusion that copper-deficiency causes disturbances in enzyme-synthesis and selective destruction of acinar cells.