Abstract

We reported previously that the pancreatic protein responses to the high dose of cholecystokinin (CCK) or bile–pancreatic juice diversion were impaired in old rats of both sexes, whereas the basal secretion was comparable to that in young animals. To examine the mechanism of the attenuated response in old rats, we examined the incidence of apoptosis of the pancreatic acinar cells and the plasma CCK concentrations produced by bile–pancreatic juice diversion, which is a potent endogenous stimulator of pancreatic secretion, in young (4–8 months old) and old (25–29 months old) rats of both sexes. Apoptosis was examined by electron microscopic examination and the nick end-labeling method for detecting cells with DNA strand breaks. The plasma CCK level was determined by RIA with OAL-656 antibody. The incidence of nick end-labeling-positive cells (apoptotic index) was slightly higher in old rats of both sexes. Apoptosis coincided with the acinar cell loss in old male rats, in which apoptotic index was much greater than that in young animals. The plasma CCK levels produced by bile–pancreatic juice diversion were lower in old than in young male rats, whereas no age difference was observed in females. The basal plasma CCK levels were comparable regardless of age and sex. The pancreatic wet weights were higher in old than in young rats of both sexes. These observations suggested that although impaired CCK functions in old male rats might have some role in the increase in apoptosis in the pancreas, the increase in apoptosis could not fully explain the attenuated pancreatic response in old rats.

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