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  • Title: Regulatory effect of glucagon on its own receptor concentrations and target-cell sensitivity in the rat.
    Author: Santos A, Blazquez E.
    Journal: Diabetologia; 1982 May; 22(5):362-71. PubMed ID: 6284578.
    Abstract:
    To evaluate the role of glucagon on its hepatocyte receptor concentrations, groups of rats were injected with a long-acting glucagon preparation (20 [G-20], 40 [G-40] or 60 [G-60] micrograms/100 g body weight) every 8 h for 4 days. Glucagon receptors in liver plasma membranes of treated animals were decreased in number (control = 1.66 +/- 0.20 ng/0.5 mg protein versus G-20 = 1.24 +/- 0.26, G-40 = 1.03 +/- 0.26, G-60 = 0.70 +/- 0.03 ng/0.5 mg protein; p less than 0.05, less than 0.001, less than 0.001, respectively), but they were indistinguishable from receptors of control rats by other criteria including affinity and kinetics of association. Degradation of both glucagon and receptor sites did not account for differences observed in binding. Similar results were obtained with isolated hepatocytes. In relation to controls, isolated hepatocytes of treated rats had a reduced number of receptors (control = 0.70 +/- 0.05 versus G-40 = 0.47 +/- 0.04 ng/10(6) cells; p less than 0.02) proportionate to the decreased glucagon-stimulated production of cyclic AMP and glucose. Four to eight hours exposure of cultured hepatocytes of nontreated rats to 4 x 10(-8) mol/l glucagon produced a decreased binding of 125I-glucagon to its receptor (p less than 0.05). In contrast, hormone exposure for shorter periods of time (0-2 h) was without effect. These results suggest (1) an inverse relationship between circulating glucagon levels and hepatocyte glucagon receptor concentration, and (2) a direct relation between receptor number and target-cell response.
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