The effect of insulin on EGF-induced cell proliferation and on modulation of EGF receptors was examined in IEC-6 cells in culture. Insulin-induced cell proliferation was not seen until concentration of the hormone reached the microgram (10 micrograms/ml) level, producing an increase in EGF receptor binding affinity (Ka 8.2 +/- .05 x 10(9)M-1 to 1.25 +/- .05 10(10) M-1). In the presence of supraphysiologic concentrations of insulin (10 micrograms/ml), EGF-induced cell proliferation could only be detected at a concentration of 50 ng/ml as opposed to a concentration of 2.0 ng/ml in the absence of insulin. This study suggests that insulin stimulates intestinal crypt cell proliferation only in supraphysiologic concentrations in a manner more characteristic of IGF-I than insulin, while producing enhanced binding of EGF to its receptor as well as an elevated threshold to EGF induced cell proliferation.
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