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The acute and chronic effects of hydrocortisone on insulin secretion were examined in the isolated perfused rat pancreas. In the first part of this study, the chronic effects of hydrocortisone on insulin release were examined using isolated perfused pancreas prepared from rats that had been given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, 5.0, and 10.0 mg/kg body weight once daily for 7 days. Hydrocortisone treatment led to a dose-dependent increase in insulin secretion in response to 8.3 mM glucose. The insulin response to 100 pM cholecystokinin (CCK-8) was also significantly higher in the hydrocortisone-treated rats than in the control group. However, the increment of insulin level over the value before CCK-8 addition in rats treated with hydrocortisone was not significantly different from that in the control rats. In the second part, the acute effects of hydrocortisone on insulin release were studied. Hydrocortisone (17-hydroxycorticosterone) at a concentration of 100 microM caused significant inhibition of the stimulatory effect of CCK-8 on insulin secretion. The inhibition started within 1 min of the beginning of hydrocortisone administration and ceased immediately after the termination of its infusion. We have demonstrated in this study a dual effect of hydrocortisone on insulin release: first, the potentiation of the insulin secretion stimulated by glucose but not by CCK-8 and, second, the inhibition of CCK-8-stimulated insulin secretion.

Pancreatic exocrine function in rats given synthetic protease inhibitor camostate (200 mg/kg body weight) perorally once daily for 10 days was investigated. Pancreatic wet weight was significantly increased in the camostate-treated rats. The increase in pancreatic weight was associated with pronounced hypertrophy and moderate hyperplasia. Total amylase, trypsin, and lipase contents in the pancreas were also increased in the camostate-treated group compared with the control rats. Secretory patterns of pancreatic juice and amylase in response to caerulein were similar in both groups, whereas the dose-response curve for pancreatic juice secretion in the camostate-treated rats was shifted tenfold toward higher concentrations of caerulein. Basal and caerulein-stimulated flow rates of pancreatic juice were significantly greater in the camostate-treated rats than the control rats, although both groups showed a threefold increase over basal secretion in response to maximal stimulation. Amylase outputs in basal state and in response to submaximal doses of caerulein were significantly lower, whereas those to maximal and supramaximal doses were significantly greater in the camostate-treated animals than that in the control rats. These results indicate that treatment with camostate induces pancreatic hypertrophy and hyperplasia, and that the secretory function of the hypertrophied pancreas is quantitatively but not qualitatively altered.