Abstract

Some actions of insulin are mediated by putative inositolphosphoglycan mediators, and a deficiency in D-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) may contribute to insulin resistance in women with polycystic ovary syndrome (PCOS). Furthermore, similar effects of DCI and metformin, an insulin-sensitizing drug, have been demonstrated in PCOS women. To determine whether metformin improves insulin actions by increasing biologically active DCI-IPG in women with PCOS, we analyzed DCI-IPG during an oral glucose tolerance test in 19 obese women with PCOS before and after 4-8 wk of metformin or placebo. After treatment, the mean (+/-SE) area under the curve (AUC) during the oral glucose tolerance test of insulin (AUC(insulin)) decreased significantly more in the metformin group, compared with the placebo group [-3574 +/- 962 vs. +1367 +/- 1021 micro IU/min.ml (-26 +/- 7 vs. +10 +/- 7 nmol/min.liter), P = 0.003], but the AUC of DCI-IPG (AUC(DCI-IPG)) decreased similarly in both groups (-1452 +/- 968 vs. -2207 +/- 1021%/min, P = 0.60). However, the ratio of AUC(DCI-IPG)/AUC(insulin) increased by 160% after metformin and decreased by 29% after placebo (P = 0.002 between groups). Moreover, metformin seemed to improve the positive correlation between AUC(DCI-IPG) and AUC(insulin) but not placebo (r = 0.32, P = 0.68 at baseline; r = 0.52, P = 0.12 after metformin; and r = -0.39, P = 0.30 after placebo). We conclude that in obese women with PCOS, metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators, as evidenced by increased bioactive DCI-IPG released per unit of insulin.