From the Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 1 242-249
Copyright © 2004 by The Endocrine Society.
-- Metformin Therapy Increases Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary Syndrome --
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 (AUCinsulin) decreased significantly more in the metformin group, compared with the placebo group [-3574 ± 962 vs. +1367 ± 1021 µIU/min·ml (-26 ± 7 vs. +10 ± 7 nmol/min·liter), P = 0.003], but the AUC of DCI-IPG (AUCDCI-IPG) decreased similarly in both groups (-1452 ± 968 vs. -2207 ± 1021%/min, P = 0.60). However, the ratio of AUCDCI-IPG/AUCinsulin 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 AUCDCI-IPG and AUCinsulin 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.
Abbreviations: AUC, Area under the curve; BMI, body mass index; CI, confidence interval; DCI, D-chiro-inositol; DCI-IPG, DCI-containing IPG; IPG, inositolphosphoglycan; NAD, ß-nicotinamide adenine dinucleotide; NADH, reduced form of NAD; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; PDH, pyruvate dehydrogenase; PDP, pyruvate dehydrogenase phosphatase.
