PACAP STIMULATES GLUCOSE OUTPUT FROM THE PERFUSED-RAT-LIVER

The effects of PACAP on hepatic glucose metabolism were examined using the flow-through perfusion method for fed rat livers, because some of the glucagon superfamily peptides stimulate hepatic glucose output. G lucose output was significantly stimulated in a dose-dependent manner by more than 1 nM PACAP-27. The potency of its stimulation was equal t o that of PACAP-38, greater than that of VIP, and clearly lower than t hat of glucagon. The cAMP output was also increased significantly by m ore than 1 nM PACAP-27; however, the degree and profile of cAMP output were not in parallel with those of glucose. Theophylline did not affe ct these stimulatory effects. On the other hand, in the perfusion expe riment with Ca2+ free perfusate, the degrees of increase in glucose ou tput induced by 15 and 40 nM PACAP-27 were significantly reduced. In c onclusion, PACAP stimulates glucose output from the perfused rat liver , and Ca2+ rather than cAMP plays an important role in this action as a second messenger.