DIURNAL PATTERN OF RAT PANCREATIC ACINAR CELL REPLICATION

Fully differentiated pancreatic acinar cells can enter the cell cycle under appropriate conditions in the rat. The aim of this study was to analyse the diurnal pattern of acinar cell proliferation as a function of food intake and the release of cholecystokinin (CCK), because the peptide hormone CCK is a major physiological regulator of rat pancreat ic acinar cell replication. Pancreatic acinar cell replication was qua ntitated using an antibody against the S-phase marker proliferating ce ll nuclear antigen (PCNA). In addition, acinar cells in S-phase were d etected after injecting bromodeoxyuridine (BrdU) and subsequent immuno histochemical staining of BrdU-positive nuclei. Rat pancreata were ana lysed during the day under standard diet conditions, as well as after various schedules of fasting and refeeding and after the application o f the CCK receptor antagonist L-364,718. Between 6 a.m. and 6 p.m., th e PCNA labeling index was 4.4+/-0.9%, while between 9 p.m. and 3 a.m. the PCNA labeling index was elevated and reached peak values of 11.4% (mean value: 7.8+/-2.5%) around midnight. BrdU-positive cells also dou bled around midnight, compared to the 9:00 a.m. value. In fasted rats, acinar cell proliferation was completely suppressed and this suppress ion could be overcome by injection of the CCK analog cerulein. In addi tion, the CCK antagonist L-364,718 led to the same results as fasting. Here we show for the first time that there is a diurnal pattern of pa ncreatic acinar cell proliferation in rats, which is dependent on food intake and is mediated by CCK.