The three major phases in the secretory process in the exocrine pancreas (synthesis, intracellular transport, zymogen discharge) have been tested in vitro after changing circulating insulin levels in rats in vivo. One group of rats received a continuous infusion of glucose for periods up to 72 hours, which keeps blood glucose levels above 200 mg/100 ml and immunoreactive insulin (IRI) raised to 130 muU/ml. As a result of this treatment, amylase content in the pancreas increases by 25% while chymotrypsinogen and lipase show a comparable decrease. The rate of total protein synthesis increased by 40% after 48 hours of infusion. The basal and carbamylcholine stimulated discharge of newly synthesized proteins are not altered. The baseline discharge of amylase is increased significantly, while the discharge of lipase and chymotrypsinogen decreased below control levels. Similar results are obtained, if circulating insulin levels are raised by the application of glibenblamide (HB419) for a period of 24 hours. Protein synthesis increases by 26.5% and baseline discharge of amylase by 50%. In chronic alloxan diabetic animals the alteration of the exocrine pancreatic function depends on the severity of the diabetes and relates to circulating insulin levels. Animals with highest blood glucose levels and low or undetectable insulin concentrations show a disappearance of amylase from the exocrine pancreas and a depression of the rate of protein synthesis by 30%. The results suggest a direct effect of insulin on protein biosynthesis and zymogen discharge, most pronounced for amylase.

Pancreatic secretion and plasma cholecystokinin (CCK) and secretin levels were measured in 10 healthy volunteers after application of a serine protease inhibitor (camostate) to study the mechanism of feedback regulation. Camostate produced a strong inhibition of trypsin and chymotrypsin activity in duodenal juice for 1 h. This was accompanied by an increase in duodenal aspirate volume and pancreatic enzyme secretion under both basal and secretin-stimulated conditions. Due to inhibition of tryptic activity, survival of lipase activity in duodenal juice was prolonged. In control experiments we ruled out that the volume and the pH of the solution were responsible for stimulation of pancreatic secretion. The protease inhibitor did not alter pancreatic secretion, which was stimulated by a test meal. Plasma levels of CCK and secretin were not changed after duodenal perfusion of camostate. These observations suggest that trypsin and chymotrypsin are involved in feedback regulation of pancreatic secretion in man which is, however, not mediated by CCK or secretin.

In this study, the cholesteryl octanoate breath test was used to monitor the release and activity of cholesterol esterase from different preparations of pancreatin in patients with severe pancreatic exocrine insufficiency. We compared treatment with acid resistant enteric coated microspheres (Panzytrat 20.000, Nordmark, FRG) to treatment with identical uncoated enzyme supplements with and without adjunctive cimetidine.

Rat dorsal prostate epithelium was studied in intact adult animals, in animals castrated for three days and in rats after inhibition of prolactin secretion. Thin sections, electron-microscopic autoradiographs and freeze-fracture replicas were used to analyze the process of apocrine secretion in this gland. The rough endoplasmic reticulum and the Golgi apparatus of the secretory cells are well developed, but secretory granules are absent. The only sign indicating release of secretory material is the appearance of blebs originating from the apical plasma membrane. Freeze-fracture replicas of the apical plasma membrane reveal that the blebs develop randomly from the bases of microvilli-like protrusions. In vitro pulse labeling of the proteins using 3H-leucine resulted in a labeling of the apical blebs. A post-castration period of three days was sufficient to reduce drastically the number and size of the apical blebs conhree weeks by application of lisuride, a synthetic ergot alkaloid, also induced regressive changes in the secretory cells. The apical blebs were still present, but they were shrunken and their content appeared condensed. These experimental conditions proved that the apical blebs are closely related to the functional activity of the cells and are interpreted as true apocrine secretion in the rat dorsal epithelium.

This report concerns a 17-year-old male patient with atypical mycosis fungoides (m.f.). Initial examination revealed generalized lymphoma and uncharacteristic livid skin efflorescence. The patient developed bone marrow involvement and meningeal leukaemia 6 months later. Diagnosis was confirmed by immunohistochemistry and electron microscopy. Aggressive chemotherapy yielded no response.