Effect of metformin on insulin binding to receptors in cultured human lymphocytes and cancer cells.

The effect of the biguanide metformin (dimethyl-biguanide) on insulin binding in vitro to IM-9 lymphocytes and MCF-7 human breast cancer cells was studied. Metformin significantly increased insulin binding to both cell types: maximum increment was 47.1 +/- 7.0% greater than control in IM-9 and 38.0 +/- 6.1% in MCF-7 cells. The dose-response curves indicated that the latter cell line was more sensitive to metformin, with a significant effect apparent at a metformin concentration of 7.7 x 10(-6) mol/l, similar to the levels reached in patients treated with this drug. When compared with phenformin, metformin was less active in increasing insulin binding to cultured cells, the ratio between the two drug responses being similar to that of their therapeutic dosage in patients. Insulin binding increment due to metformin was reversible, was not dependent on new protein synthesis and was evident also in IM-9 lymphocytes that had been down-regulated by pre-incubation with insulin (10(-7) mol/l). This effect of metformin on insulin binding to receptors may contribute to the hypoglycaemic effect of this agent in patients.