Pituitary adenylate cyclase activating polypeptide enhances glucose-evoked insulin secretion in the canine pancreas in vivo.

OBJECTIVE

To study a local effect of pituitary adenylate cyclase activating polypeptide (PACAP(1-27)) on glucose-evoked insulin release under in vivo conditions.

INTERVENTION

Glucose and PACAP(1-27) were locally infused to the pancreas via the superior pancreaticoduodenal artery without interrupting the blood supply.

MAIN OUTCOME MEASURES

Plasma insulin and glucose concentrations were determined in samples obtained from the superior pancreaticoduodenal vein and the aorta. Superior pancreaticoduodenal venous blood flow was measured to compute the net output of insulin.

RESULTS

PACAP(1-27) (0.005-5 microg) increased the basal insulin secretion by about 15 folds in a dose-dependent manner. Local infusion of either glucose (5%) or PACAP(1-27) (0.05 microg) resulted in a significant increase in the basal insulin output to about 300 microU x min(-1)g(-1), which was highly reproducible upon the second administration of the same dose with an interval of 30 min. When PACAP(1-27) was simultaneously given during glucose infusion, the increased insulin output due to glucose was further enhanced to about 600 microU x min(-1)g(-1). The net increase in PACAP(1-27)-induced insulin output in the presence of glucose was significantly greater than that obtained with PACAP(1-27) alone. There exists a strong and highly significant correlation between changes in glucose level and those in insulin output when both glucose and PACAP(1-27) were administered simultaneously.

CONCLUSION

The results indicate that PACAP(1-27) directly enhances the glucose-evoked insulin secretion in the endocrine pancreas in anesthetized dogs. The study suggests that PACAP may play a local facilitating role in insulin secretion in response to glucose loading.