The relationship between insulin binding and the inhibition of protein degradation in normal and transformed cells.

The apparent Ki for insulin binding to Reuber H35 hepatoma, rat hepatocytes, 3T3 and SV403T3 cells in monolayer culture was approximately 2 x 10(-9) M. Since insulin concentrations of 2 x 10(-12) M and 6 x 10(-11) M inhibit half-maximally intracellular protein degradation in the H35 hepatoma and SV403T3 cells respectively, it is apparent that very few insulin molecules are bound at such concentrations. The calculated number of insulin molecules bound per cell under these conditions is 45 in the H35 hepatoma and 180 in SV403T3. On the other hand, 36,000 and 2100 and molecules are bound per cell respectively at insulin concentrations which inhibit half-maximally intracellular protein degradation in hepatocytes and 3T3 cells. Measurements of insulin degradation show rates about five times greater in the H35 hepatoma as compared to hepatocytes, thus eliminating a more rapid breakdown of insulin as an explanation of the lower insulin sensitivity in hepatocytes.