:-
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-:-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??: 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.
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.
:-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.
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