Binding and biologic activity of glucagon in liver cell membranes of chronically hyperglucagonemic rats

Glucagon binding by liver cell membranes was examined in rats with chronically elevated plasma levels of immunoreactive glucagon (IRG) resulting from insulin deficiency, starvation, or twice daily glucagon injections. The concentration of specific glucagon binding sites was significantly reduced in the three chronically hyperglucagonemic (IRG > 125 pg/ml) groups as compared with nondiabetic controls and insulin-treated diabetic control rats with only mild hyperglucagonemia. A reduction in glucagon binding sites did not occur with hyperglucagonemia of 12 h or less. Despite the reduced binding of glucagon in the three chronically hyperglucagonemic groups, the ability of glucagon to stimulate cAMP production was not reduced. It is concluded that while decreased glucagon binding occurs in the forms of chronic hyperglucagonemia studied, it is not associated with a reduction in the ability of glucagon to stimulate cAMP production.