Role of Ca2+ on vasoactive intestinal peptide-induced glucose and adenosine 3',5'-monophosphate production in the isolated perfused rat liver.

Livers from fed rats (180-240 g) were perfused noncyclically with a hemoglobin-free medium in vitro to determine whether vasoactive intestinal peptide (VIP) increases hepatic glucose production through a cAMP- or a Ca(2+)-dependent mechanism. Glucose output did not increase, but cAMP increased maximally during 10(-9) M VIP infusion. When VIP was perfused at 10(-8) M or more, glucose output increased dose dependently, whereas cAMP increased only a little during the VIP infusion, but increased greatly after the infusion. When Ca2+ was excluded from the perfusate, glucose output produced by 10(-8)-10(-7) M VIP was only 40% of that observed in the Ca(2+)-containing perfusion, and the increase in cAMP was abolished almost completely. By adding 10(-7) M A23187 for 10 min during the infusion of 10(-9) M VIP, cAMP, which increased with VIP alone, decreased during the A23187 infusion and increased again after the cessation of the A23187 infusion, whereas glucose output increased during the A23187 infusion. These r...