Glucagon binding to liver membranes of Mt-T-W15 tumor-bearing and hypophysectomized rats. A possible role for insulin and growth hormone.
To assess the effect of the endocrine environment and, more specifically, of growth hormone and insulin on glucagon receptors, we studied 125I-glucagon binding to liver membranes in five groups of rats: (1) controls, (2) streptozocin (STZ)-treated, (3) tumor-bearing (growth hormone-producing, Mt-T-W15), (4) STZ-treated tumor-bearing, and (5) hypophysectomized rats. Glucagon binding was decreased in tumor-bearing, hypophysectomized, and STZ-treated rats. Basal and glucagon-stimulated cAMP levels were determined in isolated hepatocytes. The basal cAMP levels were increased in STZ-treated, tumor-bearing, STZ-treated tumor-bearing, and hypophysectomized animals. All groups responded and produced more cAMP in response to glucagon stimulation, although the maximal response was greater in STZ-treated, tumor-bearing STZ-treated, and hypophysectomized groups than in the controls. Our data confirm that hyperglucagonemia downregulates the hepatic glucagon receptors and suggest that insulin and growth hormone may play a stimulatory role in their regulation. The results also suggest that the downregulation of glucagon receptors is not directly correlated to the basal or glucagon-stimulated cAMP levels.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism / Q000502:physiology*; D007016:Hypophysectomy; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D009368:Neoplasm Transplantation; D010911:Pituitary Neoplasms / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D018027:Receptors, Glucagon
D001786:Blood Glucose; D007328:Insulin; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D013006:Growth Hormone; D005934:Glucagon; D000242:Cyclic AMP