Glucose-dependent insulinotropic action of cholecystokinin and caerulein in the isolated perfused rat pancreas.

The effect of pure natural porcine cholecystokinin (CCK) and synthetic caerulein on endocrine and exocrine pancreatic secretion was investigated in the isolated perfused rat pancreas in the presence of physiological concentrations of glucose. CCK (0.25 mU/ml) or caerulein (0.01 ng/ml) potentiated the insulin secretion induced by 5.6 mM glucose; a significant increase in pancreatic exocrine secretion was also observed at these doses of CCK or caerulein. Further increases in the concentration of CCK (0.25 to 1 mU/ml) or caerulein (0.01 to 1 ng/ml) resulted in dose-dependent increases in both insulin and pancreatic exocrine secretion. The effectiveness of CCK and caerulein as insulinotropic agents depended on the glucose concentration; they were more effective at higher concentrations of glucose. Thus, CCK or caerulein significantly and coincidentally stimulated both insulin secretion and pancreatic exocrine function if 5.6 mM or more glucose is present, whereas in previous studies using 2.8 mM glucose, stimulation of insulin secretion was elicited only with concentrations of the peptides supramaximal for an effect on pancreatic exocrine secretion. CCK may contribute to the entero-insular axis.