Effects of caerulein and trypsin inhibitors on the endocrine mouse pancreas

Oral administration to mice with soybean trypsin inhibitor (SBTI) (27-30 mg/mouse/day) or aprotinin (5500-6000 KIU/mouse/day) for six weeks increased the total pancreatic insulin (IRI). The pancreatic IRI was also increased after sc injections of synthetic caerulein (0.05 microgram/mouse/day divided into 3 daily doses), being 82% above the control levels when expressed per g pancreas. Aprotinin (6000 KIU/mouse/day divided into 3 daily doses) injected sc had no effect on the insulin content. The total glucagon did not change significantly in any of the groups, but the molar ratio of insulin to glucagon was increased in the caerulein- and SBTI-treated mice. Caerulein-treatment led to an increased disappearance rate of glucose with k-values being 7.1 +/- 0.3 compared to 6.0 +/- 0.1 (mean +/- SEM) in the controls (P less than 0.02). In islets isolated by collagenase-digestion of the pancreas and subjected to an overnight incubation, the content of insulin and glucagon was increased in islets from caerulein-treated animals. This corresponded to the results observed in the whole pancreas. The present study suggests that oral administration of proteolytic enzyme inhibitors or treatment with caerulein has a trophic effect on the endocrine pancreas. A difference in specificity seems to exist as SBTI affected both the pancreatic weight and IRI, and aprotinin orally did not influence the pancreatic weight, but increased the total content of IRI. Caerulein led to an increase in IRI, but did not affect the weight of pancreas.