ACTION OF METFORMIN ON ERYTHROCYTE-MEMBRANE FLUIDITY IN-VITRO AND IN-VIVO

The lipid domains of the cell membrane are believed to be one of the s ites where biguanides exert their antihyperglycemic effect. We have ex amined the effects of metformin on the membrane fluidity of intact ery throcytes in vivo and in vitro. Membrane fluidity was measured by moni toring changes in the anisotropy of the fluorescent probe 6-antroyloxy stearic acid (6-AS). The erythrocyte membranes from patients with non- insulin dependent diabetes mellitus treated with metformin were more f luid than those from non-insulin dependent diabetes mellitus patients treated by diet or healthy controls. There was no correlation between membrane fluidity and the plasma lipids or the parameters of metabolic control, suggesting that the high fluidity is an effect of metformin itself. Incubation of erythrocytes from healthy controls and diabetic patients treated by diet or glibenclamide with metformin in vitro conf irmed that metformin increases the fluidity of erythrocyte membranes. In vitro metformin did not alter the fluidity of membranes from diabet ic patients treated with metformin, perhaps because the basal high flu idity due to their in vivo interaction with plasma metformin could be increased no further. Since insulin appears to be required for the ant ihyperglycemic effect of metformin, the effect of insulin on membrane fluidity was also evaluated. Insulin generally had a small fluidizing effect on erythrocytes in vitro. The fluidizing action of both insulin and metformin could represent a membrane event common to the hormone and drug leading to additive or synergistic effects in vivo. (C) 1997 Elsevier Science B.V.