Increased glucagon receptors in chronically hypersomatotrophic and hyperglucagonemic rats.
The effect of increased levels of growth hormone on glucagon binding by isolated hepatocytes and on the cellular cyclic AMP response to glucagon was evaluated in rats bearing growth hormone-secreting tumor (Mt-T-W15) and in rats treated with rat growth hormone. An increased binding, due to an increased number of receptors, was observed in both groups of animals. Glucagon binding did not correlate with plasma glucagon levels, suggesting a failure of down regulation, possibly due to an effect of growth hormone and insulin on the number of receptors. Tumor-bearing and growth hormone-treated rats had larger hepatocytes so that, when hormone binding was expressed in terms of square micrometer of membrane surface, it appeared decreased. When the tumor was removed the increase in the number of glucagon receptors per cell persisted, even though the average cell size returned toward normal. It is suggested that this retention of the receptors may have been the result of continuing hyperinsulinism. Basal cAMP levels were elevated in hepatocytes of tumor-bearing and growth hormone-treated animals, possibly due to cell hypertrophy. On the other hand, the maximum cAMP response to glucagon was not altered by the experimental procedures. A negative effect of insulin on cAMP accumulation may explain this apparent paradox. Indeed, hepatocytes isolated from rats following tumor removal, but with continuing hyperinsulinemia, had a lower maximum cAMP response, even though the glucagon binding per cell or per unit of cell surface was increased.
Dunbar
J C
JC
Brown
P
P
Dixon
S
S
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000097:blood*; D013006:Growth Hormone / Q000097:blood* / Q000494:pharmacology; D006984:Hypertrophy; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D009368:Neoplasm Transplantation; D010911:Pituitary Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011920:Rats, Inbred WF; 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