Insulin and Glucagon Binding and Degradation by Kidney Cell Membranes*

Abstract

The binding and degradation of insulin and glucagon to rat kidney cell membranes was examined. Time- and temperature-dependent specific binding of [125I]iodo-insulin to kidney cell membranes was demonstrated. The membranes also degraded insulin in a time-, temperature-, and protein concentration-dependent manner. The apparent Km of the degradation was 2.7 .times. 10-7 M. Glucagon degradation by the kidney membranes was extremely active. Per milligram of protein the kidney membrane was over 20 times as active as the liver membrane. Even at 4.degree. C, significant glucagon degradation occurred. Because of this very active degradation, glucagon binding could not be accurately assessed. The kidney glucagon-degrading activity was inhibited by glutathione and EDTA but unaffected by N-ethylmaleimide, ACTH, or insulin, all potent inhibitors of liver glucagon degradation. The apparent Km for glucagon degradation by the kidney, however, was essentially identical with that for the liver, 2.4 .times. 10-6 M.