Insulin dissociation from its receptors on human fat cells. Evaluation of the negative cooperativity model.

Insulin dissociation from its receptors on isolated human fat cells was investigated using mono-125I-[Tyr A 14]-insulin. Fat cells were equilibrated with 0.05 pmol/ml of the radioligand and then transferred to a radioactive free buffer. The rate of dilution-induced dissociation of bound labelled insulin was enhanced in the presence of native insulin (1.7 nmol/ml), both at 24 degrees C and 37 degrees C and in both omental and subcutaneous adipocytes. The dissociation of radioactive insulin was more rapid when fat cells were equilibrated with 0.15 than with 0.05 pmol/ml of radioactive insulin, both in the presence or absence of an excess of native insulin. Thus, the presence of site-site interactions of the negative cooperativity type among insulin receptors of human fat cells is demonstrated.