Glucagon alters insulin binding to isolated rat epididymal adipocytes: possible role of adenosine 3',5'-monophosphate in modification of insulin action.

Effects of glucagon on insulin action in rat epididymal adipocytes were studied in vitro. [125I]iodoinsulin binding to isolated adipocytes was inhibited by preincubation of the cells with isoproterenol, epinephrine, or glucagon. Fifty percent inhibition was observed with 2 X 10(-8) M glucagon, 10(-6) M isoproterenol, and 10(-7) M epinephrine. Maximal (90%) inhibition induced by glucagon was observed at 10(-6) M. In Scatchard analysis, [125I]iodoinsulin competition data generated curvilinear plots in buffer- and glucagon-treated cells. Pretreatment of the cells with (Bu)2cAMP reduced insulin binding activity. However, the simultaneous addition of (Bu)2cAMP with [125I]iodoinsulin did not produce the inhibition of the binding when the cells were not pretreated with the agent. cAMP level in the cells was increased by incubation with glucagon. 3-O-[Methyl-3H]methylglucose uptake by isolated adipocytes was inhibited by pretreatment of the cells with glucagon. These results suggest that glucagon regulates insulin action through decrease in insulin receptor activity, and that it is possible that the inhibition is mediated by cAMP production in adipocytes.