The USDA trypsin inhibitor study. III. Sequential development of pancreatic pathology in rats

Weanling male, Wistar rats (40 per diet) were maintained on 15 diets which provided 4 graded trypsin inhibitor (TI) levels (93, 215, 337, and 577 mg/100g diet) repeated at 3 levels of protein (10%, 20%, and 30%). Raw and heated (toasted) soy flour provided 10% protein in the diet, while casein was added to increase the protein level to 20% and 30%. Three diets containing only casein as the protein source, at 10%, 20%, and 30% were included. Histologic changes occurring in the pancreas were evaluated in approximately 5 rats from each diet at 3 month intervals, beginning at 6 months, for 22 months. Criteria for the diagnosis of the observed histologic changes in the pancreas are discussed. Ultrastructure of the endocrine cells in the gastrointestinal mucosa was also examined.Pancreatic acinar cell density, as determined morphometrically, was reduced throughout the study in rats fed the 577 mg TI/100 g diet, indicating hypertrophy at the cellular level. Nodular hyperplasia was observed in the first sacrifice group at 6 months. Incidence of the lesion was positively related to both time of exposure and level of dietary TI. Acinar adenoma was first observed at 18 months and was most prevalent in rats fed the highest concentration of TI.Endocrine cells of the duodenal mucosa which contain cholecystokinin (so-called I cells) contained a denser population of secretory granules in animals fed the high TI diet compared with I cells from control animals, leading to the speculation that production and secretion of cytoplasmic hormones was increased in TI treated rats.Reference to a company and/or product named by the Department is only for purposes of information and does not imply approval or recommendation of the product to the exclusion of others which may also be suitable.