Hormonal Regulation of Pancreatic Islet Adenyl Cyclase

Adenyl cyclase activity of rat pancreatic islet membrane was increased by secretin, pancreozymin, and isoproterenol, while ACTH, glucagon, growth hormone, and insulin had no effect. Both secretin and isoproterenol activations were enhanced by prostaglandin E₁ (PGE₁) and GTP. Isoproterenol activation was additive with PGE₁, as was that of secretin with PGE₁, but only in the presence of GTP. Secretin activation in the presence of PGEi and GTP was equivalent to NaF stimulation. Kinetic analysis indicated that secretin and GTP increased the maximum velocity of the adenyl cyclase and tended to decrease the apparent affinity of the enzyme for ATP. Glucagon activation of islet membrane adenyl cyclase was dependent upon prior treatment of the membrane preparation with EGTA and the use of inhibitors of proteolytic enzymes during the collagenase digestion phase of islet preparation. These results suggest that hormonal regulation of insulin secretion may be affected by PGE₁ and guanine nucleotide modulation of the adenyl cyclase activation process.