The interaction of (125)I-labeled insulin with purified liver plasma membrane from rats fed a high fat (L) diet or a high glucose (G) diet was studied with respect to specific binding, insulin degradation, binding site degradation, and rate of hormone association and dissociation. Scatchard analysis suggested the presence of high and low affinity binding sites for membranes of both G and L diet-adapted rats. However, liver plasma membrane from rats fed the high glucose diet bound 50% more insulin than did membrane from rats fed the high fat diet. Diet did not change insulin binding site degradation. The results suggested that an apparently reduced number of insulin binding sites (G = 10.2 +/- 2.45 x 10(-12) mol/mg membrane protein, L = 4.5 +/- 1.73 x 10(-12) mol/mg membrane protein) associated with fat feeding as compared to glucose feeding was responsible for the reduced insulin binding by membrane from rats fed the high fat diet. The effects of concanavalin A (Con A) on insulin binding to liver plasma membranes were also investigated. Con A enhanced the specific binding of insulin to liver plasma membranes from rats fed either diet at concentrations lower than 50 micro g/ml, whereas at concentrations higher than 50 micro g/ml Con A inhibited insulin binding to these membranes. The stimulatory effect of Con A on insulin binding at low concentrations was greater and inhibition of binding at high concentration was less in the case of membrane prepared from L diet-adapted animals. These results suggested that diet can modify the plasma membrane glycoproteins.