Anomalous adenosine cyclic 3':5'-monophosphate responses to glucagon in patients with hepatocellular carcinoma

Glucagon resistance has been reported in rat hepatoma models. We studied the responses to glucagon challenge in 35 patients with hepato-cellular carcinoma. They have increased cyclic AMP and decreased glucose responses to glucagon (2 mg) challenge when compared with normal controls. Possible explanations for increased cyclic AMP responses include special membrane properties of hepatoma cells and increased adrenergic stimulation of adenylate cyclase during hypoglycemia. Decreased glucose responses are most apparent in patients with overt hypoglycemia. This may be related to a number of postulates, including depleted glycogen store of liver, impaired glycogenolysis, fatty metamorphosis, or insulin-like activities secreted by hepatoma. In this study, the increased cyclic AMP responses do not support the postulation that glucagon receptors are damaged in hepatocellular carcinoma.