Myoinositol system

:-What is myoinositol System? Inositol is a polyalcohol existing in as many as nine different isomers of which two isomers (namely MI &DCI) are relevant in human reproduction. These are basically insulin sensitizers but other actions as well in most organs of body. MI preferentially corrects Menst irregularities and it (MI= Myoinositol) is more mature isoform metabolically. Till date it appears from diff studies that treatments of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2 g twice/day

What is D-Chiro-inositol (DCI)? By contrast DCI is mainly formed inside the body by the process of epimerization   by the enzyme epimerase. Genetic deficiency of such enzyme may adversely affect oocyte quality. This is akin to endogenous synthesis of L-Methyl -Folic Acid & failure of methyl donation process. Physiological blood ratio is important for many functions in the body. But each organ in human body is tuned their own set MI: DCI ratio for glucose utilization.

Obese PCOS & DCI:-What other information we have at the moment on DCI at our disposal?? Women with the polycystic ovary syndrome have insulin resistance and hyperinsulinemia, possibly because of a deficiency of a d-chiro-inositol–containing phosphoglycan that mediates the action of insulin. We hypothesized that the administration of d-chiro-inositol would replenish stores of the mediator and improve insulin sensitivity

DCI-Last minute suggestion:-It is also claimed that DCI:- D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations

In IVF??? Relevance of supplementing MI & DCI routinely 12 weeks prior to IVF-ET-Well, some considers these drugs worthy in such indication.

MI a friend or foe in obese PCOS??? What benefits they do? Current researches on the topics the relation between such polyalcohol (inositol family) and diseases like metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes.

“All said—all done”: But what happens at Ovarian Level? What MI does at Go Cell Level??

MI-by the enzyme epimeraseà converted to DCI at ovariesàrelative deficiency of MI at ovaries and Follicular fluid in particular in women suffering from excessive enzymatic activity of  epimerase-> impaired FSH signalling due to lack of FSH signalling at Go Cells & also maturing Oocyte. Both MI and Melatonin in optimum level help in achieving good quality oocytes. In fair number of PCOS women there is +ve response by OV induction   drugs but fertilization fail to occur due to poor quality of oocytes which is not reflected in Non-ART cycles . I mean USG tracking may be unable to qualify the fertilizing capability of Oocytes –Mitochondrial    damage induced by deficient MI and or Melatonin or both. Some of the actions of insulin may involve low-molecular-weight inositol phosphoglycan mediators.

What happens when??  What happens when 4 Apples are lost from a basket and the remaining apple numbers to  = 100? What were the originally total apples in the basket? Back to math of class III :When insulin binds to its receptor, mediators of this class are generated by hydrolysis of glycosylphosphatidylinositol lipids located at the outer leaflet of the cell membrane. Released mediators are then internalized and affect intracellular metabolic processes. Although different species have been identified, an inositol phosphoglycan molecule containing d-chiro-inositol and galactosamine is known to have a role in activating key enzymes that control the oxidative and no oxidative metabolism of glucose.

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A deficiency of the d-chiro-inositol phosphoglycan –How best to counteract? A deficiency of the d-chiro-inositol phosphoglycan mediator of the action of insulin may result in resistance to insulin. Insulin resistance has been linked to decreased urinary excretion of chiro-inositol (a component of the putative d-chiro-inositol phosphoglycan mediator) in primates, in humans with impaired glucose tolerance or type 2 diabetes mellitus, and in nondiabetic first-degree relatives of persons with diabetes. The amount of chiro-inositol in muscle is lower in subjects with type 2 diabetes mellitus than in normal subjects.

 In a study of rats, administration of d-chiro-inositol decreased hyperglycemia in rats with diabetes and improved glucose tolerance in normal rats. In a study of monkeys with varying degrees of insulin resistance, d-chiro-inositol accelerated the disposal of glucose and decreased insulin secretion.These observations suggest that the administration of d-chiro-inositol, which is then presumably used in the formation of the active d-chiro-inositol phosphoglycan mediator, may increase insulin sensitivity and improve the action of insulin in insulin-resistant subjects.

Slightly elevated level of MI is more congenital / helpful for proper oogenesis:-Elevated concentrations of myo-inositol in human follicular fluids appear to play a positive function in follicular maturity and provide a marker of good quality oocytes.

Nevertheless its positive role in PCOS women is a consequence of a defect in the insulin signaling pathway (inositol-containing phosphoglycan mediators) that seems to be primarily implicated in the pathogenesis of insulin resistance

 Like Vit D deficiency in men & women of a milkmaid home - Is kidney at fault in Obese PCOS women?  We are aware that active Vit D3 is synthesize at Kidneys –therefore it’s not surprising that family members of milkmaid home may essay a victim of Vit D deficiency. Possibly yes. Because there is excess urinary clearance of DCI (six times more urinary excretion) in PCOS women. So relative blood deficiency of DCI=altering the available blood ratio between MI & DCIàaltered insulin signalling and impaired FSH signalling too.

How to identify cases that will be benefited by MI monotherapy? No such lab test available till date. But fact is these two polyalcohols act as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework.

 Let me stop here as you are snoring:-With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice.