Inositol as putative integrative treatment for PCOS

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Inositol as putative integrative treatment for PCOS Alessandro D. Genazzani Reproductive BioMedicine Online Volume 33, Issue 6, Pages 770-780 (December 2016) DOI: 10.1016/j.rbmo.2016.08.024 Copyright © 2016 Reproductive Healthcare Ltd. Terms and Conditions

Figure 1 Schematic pathway from d-glucose-6-phosphate to d-chiro-inositol. The limiting enzyme is the epimerase (modified from Larner et al., 2010). Reproductive BioMedicine Online 2016 33, 770-780DOI: (10.1016/j.rbmo.2016.08.024) Copyright © 2016 Reproductive Healthcare Ltd. Terms and Conditions

Figure 2 Schematic representation of insulin signalling proposed by Larner et al. (2010). Insulin binding to its receptor (IR) activates a signal via two different and parallel pathways. In the first pathway, the substrates of the insulin receptor (IRS) activate various proteins (PI3K, PDK, PKB/Akt), and PKB/Akt induces glucose transporter 4 (GLUT-4) translocation to the plasma membrane to upload glucose. In the second pathway IR via a G protein (Gp) coupled to a phospholipase D (PLD) causes the hydrolysis of a glycosyl phosphatidylinositol (GPI), which releases an inositol phosphoglycan containing d-chiro-inositol, which acts as second messenger of insulin (INS-2). Then INS-2 enhance glucose storage (GS) as glycogen in the cytosol and also glucose oxidative use in the mitochondria. GSK3 = Glycogen synthase kinase 3; PDH = pyruvate dehydrogenase; PDHP = pyruvate dehydrogenase phosphatase; PDK = phosphoinositide-dependent kinase; PI3K = phosphoinositide 3 kinase; PKB/Akt = protein kinase B/Akt; PP2Ca = phosphoprotein phosphatase 2C alpha (modified from Croze and Soulage, 2013). Reproductive BioMedicine Online 2016 33, 770-780DOI: (10.1016/j.rbmo.2016.08.024) Copyright © 2016 Reproductive Healthcare Ltd. Terms and Conditions

Figure 3 Myo-inositol (MYO) is usually converted to d-chiroinositol (DCI). The MYO to DCI ratio in the urine of controls is completely different from that observed in patients with type 2 diabetes, in non-diabetic relatives, and in patients with type I diabetes (modified from Larner and Craig, 1996 and Croze and Soulage, 2013). Reproductive BioMedicine Online 2016 33, 770-780DOI: (10.1016/j.rbmo.2016.08.024) Copyright © 2016 Reproductive Healthcare Ltd. Terms and Conditions