Secretin-Induced Exocrine Secretion in Perfused Pancreas Isolated From Diabetic Rats

Exocrine secretory function in response to 10 pM to 10 nM synthetic secretin was evaluated in perfused pancreas isolated from control, streptozocin-induced diabetic (STZ-D), alloxan-induced diabetic (ALX-D), and insulin-treated STZ-D rats. In STZ-D rats, the basal rate of pancreatic juice flow was significantly increased (10.3 ± 1.0 μl/20 min) compared with control rats (4.4 ± 0.2 μl/20 min). The basal rate of amylase output as well as pancreatic amylase content were significantly decreased to <5% of control values. The basal rates of protein and trypsinogen outputs were similar in both groups. In both control and diabetic rats, secretin caused a dose-dependent increase in exocrine secretion. Secretin (10 pM to 10 nM) induced 1.1- to 11.7-fold increases in exocrine secretion in STZ-D rats. These increases were significantly lower than the 2.1- to 20.8-fold increases in control rats. Furthermore, there was no significant increase in exocrine secretion from STZ-D rats in response to 10 pM secretin, although this concentration of secretin caused a significant increase in control rats. Secretin-induced exocrine secretion in ALX-D rats was similar to that in STZ-D rats. In insulin-treated STZ-D rats, the basal rates of pancreatic secretion were not significantly different from those of control rats. Secretin, at a concentration of 10 pM, caused a significant increase in juice flow (from 8.6 ± 1.6 to 30.7 ± 2.0 μl/20 min), protein output (from 227.9 ± 47.3 to 661.0 ± 127.5 μg/20 min), and trypsinogen output (from 37.4 ± 5.3 to 125.8 ± 27.6 μg/20 min), but not in amylase output (from 247.9 ± 57.2 to 327.4 ± 80.6 Somogyi units/20 min). Pancreatic juice flow from insulin-treated STZ-D rats in response to 10 nM secretin (40.3 ± 2.0 μl/20 min) was similar to that of control rats (46.5 ± 5.5 μl/20 min), whereas protein and enzyme outputs in response to 10 nM secretin were significantly reduced compared with those of control rats. This study indicates, therefore, that the sensitivity to secretin is reduced in the diabetic rat pancreas. In addition, this change is, in part, reversible by insulin treatment.