The influence of an absorbable
glucosidase inhibitor (
Bay o 1248) on the endocrine and exocrine rat pancreas was evaluated. Rats fed a standard diet containing
Bay o 1248 over 10 days consumed less food, gained about 30% less
body weight than controls and showed meteorism. In these animals postprandial plasma
insulin and
glucose levels were decreased, but the total pancreatic
insulin content was not different versus controls. The early
insulin secretory response studied by pancreas perfusions was found reduced after a stimulatory
glucose load (10 mM). Addition of the
glucosidase inhibitor (1 mM) to the incubation medium diminished the
glucose-induced
insulin release from isolated islets of rats fed a standard diet. The compound added to the perfusion medium (10 microM) induced a slight reduction of half-maximal
glucose-induced (10 mM)
insulin release from the perfused pancreas. This inhibitory effect disappeared during maximal stimulation (20 mM
glucose) of insulin secretion. The compound neither altered basal nor
arginine-induced (15 mM)
insulin release from the perfused organ. The exocrine pancreas was studied after feeding a Bay o 1248-enriched standard diet over 10 days.
Amylase and
trypsin concentration and total output into the biliary-pancreatic juice in response to CCK and
secretin (20 IU or CU/kg
body weight each) were diminished. The pancreatic
enzyme content did not differ compared to controls. A significant role of
carbohydrate maldigestion, systemic effects of the
glucosidase inhibitor, and endocrine-exocrine pancreatic interrelations are discussed to account for the effects of the compound on the rat pancreas.