NEW CHRONIC-PANCREATITIS MODEL WITH DIABETES-INDUCED BY CERULEIN PLUSSTRESS IN RATS

To establish a new experimental model of chronic pancreatitis (CP) wit h diabetes, we investigated pancreatic endocrine function, blood flow, and histopathology in CP induced by repetition of cerulein injection plus water immersion stress in rats, CP rats were treated with water i mmersion stress for 5 hr and two intraperitoneal injections of 20 mu g /kg body weight of cerulein once a week for 16 weeks. In the CP group, pancreatic contents of protein, amylase, elastase, and lipase signifi cantly decreased to 64, 38, 23, and 68% of the control group, respecti vely. In oral glucose tolerance test (glucose 2 g/kg body wt), blood g lucose level in the CP group was 212.1 +/- 97.8 mg/dl (mean +/- SD) at 30 min and was significantly higher than the control group (126.3 +/- 15.4 mg/dl) (P < 0.05). Two of seven rats in the CP group showed an o bvious diabetic pattern with a blood glucose level over 200 mg/dl at 1 20 min. The basal level of serum insulin in the CP group was 640.1 +/- 148.7 pM, significantly lower than in the control group (1133.4 +/- 2 42.0 pM) (P < 0.001). However, insulin content in the pancreas was 12. 37 +/- 1.72 nmol/pancreas and was preserved compared with the control group (10.24 +/- 1.94 nmol/pancreas). In CP rats, winding and dilatati on of surface blood vessels and gland atrophy were evident. Marked fib rosis, fatty changes, and destruction of lobular architecture were als o demonstrated microscopically, although the structure of each pancrea tic islet was preserved and each islet was fully stained with anti-ins ulin antibody. In the CP group, pancreatic blood flow by the hydrogen gas-clearance method was 197.6 +/- 33.0 ml/min/100 g, which was signif icantly less than the control group (276.2 +/- 19.1 ml/min/100 g) (P < 0.001), Thus, we conclude that the CP model induced by cerulein plus stress is a new CP model with diabetes in rats, in which the glucose t olerance was impaired without loss of insulin reserve.