The USDA trypsin inhibitor study. II. Timed related biochemical changes in the pancreas of rats

A total of 600 rats was distributed equally among 15 diets formulated from mixtures of raw and toasted soy flour and casein so as to provide 5 different levels of trypsin inhibitor (TI) at 3 levels of protein (10%, 20%, and 30%). Animals were sacrificed at the end of 6 months and at 3-month intervals thereafter over a period of 22 months. Increases in the secretory activity of the pancreas, as measured by trypsin and chymotrypsin activities in the pancreas and small intestines, were associated with increasingly higher levels of TI and protein but did not change appreciably with time. Hypertrophy and hyperplasia of the pancreas, as reflected by changes in pancreas weight and RNA and DNA content, developed at an early stage (6 months) and were likewise positively correlated with the levels of TI and protein in the diet. Although the hypertrophic response remained unchanged with time, hyperplasia became more pronounced as the period of exposure to TI was prolonged. The peptide test confirmed the stimulatory effect of TI on the pancreas, but some functional impairment was noted in those animals which had been fed raw soy flour for 18 months of or longer. The appearance of nodules on the pancreas was observed by gross inspection after 15 months, and these became larger and more numerous with time. The incidence of nodules was highly correlated with the level of TI in the diet and was highest when the diet contained 20% protein.