Myoinostol lack is the cause of PCO ,hyperinsulinaemic PCO in particular.

Believe me or not!!!

Q. 1: Hypothesis No 4 of development of Frank DM?? How responsible is Myoinisitol deficiency?? Why does DM occurs at all Intracellular depletion of MI is one of the mechanism of development PCO & later DM!!

 This view has been upheld by many scientists is that “ insulin-sensitizing effect of a MI and DCI supplementation operates in body favourably in some not all DM cases ??” :-Arguments : The explanation is like this. Inhibition of cellular Myo(myoinositol) uptake, altered MI biosynthesis, enhanced MI efflux due to sorbitol intracellular accumulation happens in fair number of Insulin resistant men & women. To correct that as we are unable to gene therapy now  we can suppl Myo from exogenous route as tablet/Sachet or MD sachet.  Additionally,  , an increased MI degradation are the possible putative mechanisms of depletion of  MI inside the cells resulting in PCO--?later DM as there is minimal glucose entry inside the cells .

Q.2:- Myo helps in synthesis of second messenger for glucose transport inside the cells :-Then let us what is   inositol glycan insulin second messengers?? Ans:- The insulin-sensitizing effect of a MI and DCI supplementation is probably due to their intracellular enhanced availability for the production of membrane IPG pre­cursors; numerous evidences support the hypothesis of a role of inositol glycan insulin second messengers in insulin-mimetic properties of some inositol isomers. Moreover, it is known that part of MI supplementation effect on insulin sensiti­vity may come from its partial in vivo intracellular epimerization to DCI .

MI intracellular concentration is regulated through processes such as extracel­lular MI uptake, de novo MI biosynthesis, MI regeneration, Myo efflux, and Myo degradation. All are running with dagger to destroy the conc of Myo inside the cells of IR PCO women .Alteration of one or several of these processes can lead to inositol intracellular abnormalities in diabetes mellitus. To summarize there is intracellular Myo depletion and that what is exactly is corrected when we supplement Myoinositol in  PCO cases with insulin resistance.

.Q.3;-Examine the urine of PCO women and prescribe Myo with confidence. No CPA, I assure you.What happens in urine of a PCO women who had less Myo??  Ans: There is a a decreased urinary excretion of DCI and an increased urinary excretion of MI in humans with type II diabetes (ten times higher compared to healthy subjects.) . Altered ratios of increased myoinositol to decreased D-chiro-inositol in urine have even been proposed as an index of insulin resistance in humans. Excessive urinary MI excretion could reduce MI plasma level and subsequently emphasize MI intracellular depletion, particularly in tissues heavily dependent on extracellular MI import. Researchers have  proposed that, in a woman with PCOS, an initial genetic or environmental insult causing insulin resistance leads to a compensatory hyperinsulinemia. The latter induces a defect that increases renal clearance of DCI, and this leads to a reduction in circulating DCI and its availability to tissue.

Q.4  What happens in normal women?? Researchers have time and again shown that when plasma glucose is maintained at stable levels and plasma insulin is acutely raised and maintained at constant levels, the circulating DCI-LPG insulin mediator is released rapidly and briefly in normal women. Conversely, this coupling between insulin action and DCI-IPG release was entirely absent in obese women with PCOS: the release of bioactive DCI-IPG was significantly lower in obese PCOS women .

Q.5:- ABC of Myo / DCI in second semester:  Organ specific epimerase!!!!  The epimerase enzyme is gene guided but surprising there is unequal distribution of epimerase in diff organs of human body, not forgetting ovaries!! Do U believe this old man??? Organ specific epimerase!!!! I hope members knew this.  Epimerase is the lead cause of CORONA epidemic (PCO):-The ratio of MU/ DCI is regulated by an epimerase that converts MI into DCI and surprisingly we the poor gynacologists are unaware of the fact that each organ has a specific Myo/ DCI ratio to which that organ is accustomed. A deficit in MI to DCI epimerization activity, due to an abnormal epimerase-type enzyme, has been postulated.

Q.6:- Abnormal epimerase in a given tissue: - Then?? Ans: - Decreased production of DCI from MI reduces the availability of intracellular DCI for its incorporation into IPGs (particularly, DCI­IPG), probable downstream second messengers of insulin. Furthermore, the decreased DCI content in insulin target tissues could reduce insulin signal transduction involving IPGs, in order to contribute to insulin resistance in those tissues.

Q. 7 :-What happens in PCO?? Ans:-Depleted plasma levels of DCI observed in PCOS patients underline the correlation between impaired plasma DCI and insulin resistance

Thus, insulin resistance is associated with:

1)                   Abnormally low levels of DCI in urine, plasma, and insulin target tissues (liver, muscle, fat)

2)  Excessive MI urinary excretion

3)  Intracellular MI deficiency in insulin-sensitive tissues. The consequence is an intracellular deficiency of DCI and of DCI-IPG, a mediator of insulin action. Diminished release of DCI-IPG in response to stimulation by insulin results in a further decrease in insulin sensitivity

QPossible explanations for these findings are a deficit in intracellular DCI or DCI­IPG and/or a defect in incorporation of the substrate DCI with membrane phospho­glycans to generate DCI-IPG mediator

The possibility that a deficit in circulating DCI, or its precursor MI, is responsi­ble for defective insulin-stimulated release of DCI-IPG mediator in PCOS is sup­ported by the findings that oral supplementation with DCI -MI to both lean and obese PCOS women improved their insulin resistance and clinical symptoms.

Moreover, defective DCI-IPG release in response to insulin could be due to a qualitative (rather than quantitative) defect in the insulin signaling mechanism that activates DCI-IPG mediator release from the membrane: there may be a primary defect in the union of the insulin receptor I3-unit to the G protein or a defect in G-protein activation of phospholipase C.

This observation fits with Cheang et al. data they showed, in a number of hyperinsulinemic PCOS patients who did not respond to DCI treatment, the absence

Insulin action mediator

MI and DCI alteration in insulin resistance, proposed by Lamer of changes in DCI-IPG release suggesting that a functional defect rather than a simple inositol nutritional deficiency might be present

Inositol as Treatment for PCOS

A supplementation with myoinositol or D-chiro-inositol was found to be safe and
effective, in improving metabolic and hormonal parameters in PCOS ain m of action is based on improving insulin sensitivity of target tissues

Insulin sensitivity

resulting in the reduction of insulinemia which has a positive effect on the reproduc­tive axis and metabolism.

One of the first studies was conducted in 1999 by Nestler et al  who found that the administration of D-chiro-inositol to women with polycystic ovary syndrome decreased the insulin response to orally administered glucose; simultaneously with the reduction in insulin secretion, women who received DCI had a significant improve­ment in ovulatory function and decreased serum androgen concentrations

It was demonstrated in various studies that both DCI and MI are able to:

·         Reduce LH levels, LH/FSH ratio, and testosterone levels

·         Restore spontaneous ovulation and menstrual cycles,

·         Improve cutaneous disorders of hyperandrogenism, reducing hirsutism and acne score