Glucagon-stimulable adenylyl cyclase in rat liver. The impact of streptozotocin-induced diabetes mellitus

Astract. The effects of chronic uremia and glucagon administration on glucagon-stimulable adenylyl cyclase in rat liver were assessed by determinations of adenylyl cyclase activities, specific iodoglucagon binding, and the activity of the stimulatory regulatory component of adenylyl cyclase. Glucagon-stimulated adenylyl cyclase was reduced in uremia to 75-80 % of control levels (P < 0.05), in the presence or absence of saturating levels of guanosine triphosphate (GTP) and 5'-guanylylimido-diphosphate [GMP-P(NH)P]. Although these changes were accompanied by a concomitant 20 % reduction in sodium fluoride-stimulated activity, basal, GTP-, GMP-P(NH)P-, and manganese-dependent adenylyl cyclase activities were unchanged. Using [125I-Tyr'0]mono-iodoglucagon as a receptor probe, the number of high affinity glucagon-binding sites was reduced 28 % (P < 0.01) in uremic as compared with control liver membranes. However, the affinity ofthese binding sites was unaltered. The S49 cyC-reconstituting activity with respect to both GMP-P(NH)P- and isoproterenol plus GTP-stimulable adenylyl cyclase was unaltered in membranes from uremic as compared with control rats. Intermittent glucagon (80-100,g) injections administered at 8-h intervals to normal rats reproduced all ofthe above described effects ofchronic experimental uremia on the adenylyl cyclase system. It is concluded that changes in the hormone-stimulable ad-Address all reprint requests to Dr. Garber. Receivedfor publication 22 December 1982 and in revisedform 2