Effect of Metformin on Tyrosine Kinase Autophosphorylation of Erythrocyte Insulin Receptor from Women with Polycystic Ovary Syndrome

ObjectiveTo document the possible effect of tyrosine kinase autophosphorylation on erythrocyte insulin-receptor after 12 weeks of metformin administration from the women with polycystic ovary syndrome (PCOS).MethodsThirty non-obese (BMI<25 kg/m2) healthy women with normal reproductive cycles were evaluated by conventional criteria as the control, 30 non-obese women with PCOS were categorized as nob-PCOS group, 40 obese women with PCOS (BMI ⩾ 25 kg/m2) were categorized as ob-PCOS group. Subjects with PCOS were given metformin 850 mg/d for 12 weeks. The autophosphorylation of insulin receptor pY1158, pY1162/1163 and insulin receptor-β subunit (IR-β) from the solubilised erythrocyte were detected by ELISA.Results1) Only the autophosphorylation level of pY1158 in nob-PCOS and ob-PCOS groups was lower (P<0.05) than that in control group and it can be increased after insulin stimulation (P<0.05); no similar changes were found in pY1162/1163 (P>0.05), even insulin-stimulated insulin receptor (P>0.05) from both of PCOS groups. 2) After metformin administration, the pY1158, pY1162/pY1163 autophosphorylation levels were increased (P<0.01) and further increased after plus insulin stimulation in vitro (P<0.01). The pY1162/1163 autophosphorylation level was increased in nob-PCOS group (P<0.01) and ob-PCOS group (P<0.05). 3) No difference was found in concentration of IR-β between control group and both of PCOS groups following metformin administration (P>0.05). In summary, oral administration of metformin led to an significant increase in tyrosine kinase activity in both groups of PCOS.ConclusionThe impairment of tyrosine autophosphorylation at pY1158 may contribute to insulin resistance, the tyrosine kinase activity per receptor of solubilised erythrocytes were significantly increased by metformin administration and the effect of metformin on insulin-receptor tyrosine kinase activity appeared to be independent of either of these variables.