Insulin-stimulated receptor phosphorylation appears normal in cultured Epstein-Barr virus-transformed lymphocyte cell lines derived from patients with extreme insulin resistance.

Insulin-stimulated phosphorylation of the insulin receptor was studied in cultured B-lymphocytes transformed by Epstein-Barr virus. In studies with cell lines derived from six normal subjects, insulin (10(-7) M) caused an average increase of approximately 200% in 32P incorporation into the 95K subunit of the insulin receptor. Phosphorylation was rapid (detectable within 1-2 min) and reached a maximum level by 15 min. Dose-response curves for receptor occupancy and phosphorylation were nearly superimposable, indicating few or absent spare receptors for this response to insulin. These data suggest that insulin receptor phosphorylation is an early response to insulin in cultured lymphocytes transformed with Epstein-Barr virus. We studied insulin receptor phosphorylation in cell lines derived from nine patients with clinical syndromes associated with extreme insulin resistance, all of whom had normal [125I] insulin binding. While the magnitude of insulin's stimulation varied widely among the individual cell lines, no significant differences were found between cell lines from normal subjects and those from patients with extreme insulin resistance.