Role of inositolphosphoglycan mediators of insulin action in the polycystic ovary syndrome.
Evidence suggests that some actions of insulin are mediated by putative inositolphosphoglycan (IPG) mediators, also known as second messengers. We review studies indicating that the IPG signaling system transduces insulin's stimulation of human thecal androgen biosynthesis, thus offering a mechanism by which insulin can stimulate ovarian androgen production even in women with PCOS whose tissues are resistant to insulin's stimulation of glucose metabolism. Furthermore, a deficiency in a specific D-chiro-inositol-containing IPG may contribute to insulin resistance in women with PCOS. In support of this idea, administration of D-chiro-inositol has been demonstrated to improve glucose tolerance, decrease serum androgens and improve ovulation in PCOS. The hypothesis is advanced that PCOS may be characterized by a defect in the conversion of myo-inositol to D-chiro-inositol, and that such a defect would contribute to both insulin resistance and hyperandrogenism in the syndrome.
Nestler
J E
JE
Department of Medicine, Medical College of Virginia, Virginia  Commonwealth University, Richmond 23298-0111, USA. nestler@hsc.vcu.edu
Jakubowicz
D J
DJ
Iuorno
M J
MJ
D000728:Androgens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives / Q000627:therapeutic use; D007295:Inositol Phosphates; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D009844:Oligosaccharides / Q000502:physiology*; D010053:Ovary / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D011134:Polysaccharides
D000728:Androgens; D007295:Inositol Phosphates; D007328:Insulin; D009844:Oligosaccharides; D011134:Polysaccharides; C028039:inositol phosphate glycan; D007294:Inositol