D-chiro-inositol Research Articles

Хемореактомный анализ стереоизомеров инозитола: различные профили фармакологического действия мио-инозитола и D-хиро-инозитола при нарушениях женской репродуктивной системы

Inositol-containing drugs (stereoisomers of cyclohexane-1,2,3,4,5,6-hexol) are used to compensate insulin resistance, particularly in patients with menstrual and ovarian disorders. Inositols are effective in preventing folate-resistant fetal malformations. Objective. To analyze pharmacological differences between the four main biologically active stereoisomers of inositol: myoinositol (MI), D-chiro-inositol (DCI), neo-inositol (NI), and scylloinositol (SCI) using the comparative chemoreactomic method. Materials and methods. Chemoreactom analysis, PubChem / PHARMGKBb HMDB, STRING databases Results. DCI is more sufficient than MI for (1) processing of branched-chain amino acids, which promotes normalization of glucose metabolism, as well as (2) metabolism of folates, vitamin PP, vitamin B5, and magnesium, (3) activation of insulin-like growth factor 1 (IGF-1) receptor, whose activity is important for the prevention of sarcopenia, (4) antitumor effects (by inhibiting hyperproliferative effects, including those associated with excess glucose and an imbalance of androgens and estrogens), (5) inhibition of proinflammatory proteins (matrix metalloproteinase 15, ICAM1, and IRAK4 that mediate effects of interleukin-1). Conclusion. The profiles of pharmacological activity of DCI and SCI differ significantly from those of MI and NI. Therefore, combinations of MI and DCI are a more promising option to increase the sensitivity of cells to insulin than separate use of MI or DCI. Key words: insulin resistance, hyperandrogenism, polycystic ovary syndrome, post-genomic pharmacology, myo-inositol, D-chiro-inositol, neo-inositol, scylloinositol, Dikirogen

Новые возможности интегративной терапии пациенток с синдромом поликистозных яичников и нарушениями углеводного и липидного обмена. Результаты сравнительного исследования

Background: long-term combined estrogen-progestin oral contraceptive pills (COCPs) are the first-line treatment for polycystic ovary syndrome (PCOS). However, this therapeutic option does not affect metabolic disorders that are more severe in women with the second PCOS phenotype thus increasing the risk of cardiometabolic complications.Aim: to assess the effect of myo-inositol and D-chiro-inositol at a 5:1 ratio on metabolic parameters in women of reproductive age with the second PCOS pathogenetic type and the disorders of carbohydrate and lipid metabolism. Patients and Methods: 60 overweight and obese women with PCOS were enrolled in this randomized prospective study. Group 1 women (n=30) received COCP and a drug containing two isoforms of inositol at a 5:1 ratio (myo-inositol 1,000 mg plus D-chiro inositol 200 mg). Group 2 women (n = 30) received COCP only. Hemostasis, lipid panel, fasting glucose level, body mass index (BMI), and waist circumference were measured before and 90 days after treatment begins. Results: in group 1, the significant (p<0.05) improvement of lipid parameters was reported as demonstrated by the reduction of the levels of total cholesterol (TC) by 16.9%, triglycerides by 15.7%, low-density lipoprotein cholesterol (LDL–C) by 17.8%, fibrinogen by 15.8%, and fasting glucose by 16.9% as well as the increase of high-density lipoprotein cholesterol (HDL–C) by 28.5%. Meanwhile, no significant changes were seen in group 2. Additionally, the reduction of waist circumference by 4.5% and BMI by 9.1% was reported in group 1. Conclusions: a medication containing myo-inositol and D-chiro-inositol at a 5:1 ratio is promising for the prevention of cardiometabolic complications in women with PCOS. Further large studies of the investigated drug are needed to demonstrate its efficacy and to assess its properties. KEYWORDS: polycystic ovary syndrome (PCOS), treatment, prevention, obesity, metabolic syndrome, lipid panel, inositol, oral contraceptive pills. FOR CITATION: Dobrokhotova Yu.E., Lapina I.A., Chirvon T.G., Taranov V.V. New prospects of the integrative therapy for polycystic ovary syndrome in women with the disorders of carbohydrate and lipid metabolism: a comparative study. Russian Journal of Woman and Child Health. 2020;3(3):169–173. DOI: 10.32364/2618-8430-2020-3-3-169-173.

Inositols' Importance in the Improvement of the Endocrine-Metabolic Profile in PCOS.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility and metabolic problems among women of reproductive age. The mechanism of PCOS is associated with concurrent alterations at the hormonal level. The diagnosis assumes the occurrence of three interrelated symptoms of varying severity, namely ovulation disorders, androgen excess, or polycystic ovarian morphology (PCOM), which all require a proper therapeutic approach. The main symptom seems to be an increased androgen concentration, which in turn may contribute to different metabolic disorders. A number of papers have demonstrated the significant role of inositol therapy in PCOS. However, there is a lack of detailed discussion about the importance of myo-inositol (MI) and d-chiro-inositol (DCI) in reference to particular symptoms. Thus, the aim of this review is to present the effectiveness of MI and DCI treatment for PCOS symptoms. Moreover, the review is focused on analyzing the use of inositols, taking into account their physiological properties, together with the mechanism of individual PCOS symptom formation.

High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial

The aim of this study was to evaluate the effect of two doses of d-chiro-inositol (DCI) in combination with Myo-inositol (MYO) on the oocyte quality (OQ) of women with polycystic ovarian syndrome (PCOS) undergoing intracytoplasmic sperm injection (ICSI). Methods: This was a controlled, randomized, double-blind, parallel group study on 172 oocytes from 11 women. The study compared the effect of two MYO-DCI formulations given over 12 weeks on OQ. Five women received 550 mg of MYO + 300 mg of DCI daily (high DCI content group), while 6 women were given a daily dose of 550 mg of MYO with the only 27.6 mg of DCI (low DCI content group). Results: According to a multivariate analysis using linear mixed effect models, high doses of DCI have a positive influence on the quality of the cytoplasm of the oocyte (β = 1.631, χ2 = 7.347, d.f. = 1, p = .00672). Zona pellucida, plasma membrane, cytoplasm, and sperm reception have also been improved with any combination of MYO/DCI by decreasing testosterone or improving insulin sensitivity, regardless of age and body mass index. Conclusion: The combination of MYO with high doses of DCI improved oocyte cytoplasm quality in women with PCOS undergoing ICSI.

Myo-Inositol and Its Derivatives: Their Emerging Role in the Treatment of Human Diseases.

Myo-inositol has been established as an important growth-promoting factor of mammalian cells and animals. The role of myo-inositol as a lipotropic factor has been proven, in addition to its involvement as co-factors of enzymes and as messenger molecules in signal transduction. Myo-inositol deficiency leads to intestinal lipodystrophy in animals and “inositol-less death” in some fungi. Of late, diverse uses of myo-inositol and its derivatives have been discovered in medicinal research. These compounds are used in the treatment of a variety of ailments from diabetes to cancer, and continued research in this direction promises a new future in therapeutics. In different diseases, inositols implement different strategies for therapeutic actions such as tissue specific increase or decrease in inositol products, production of inositol phosphoglycans (IPGs), conversion of myo-inositol (MI) to D-chiro-inositol (DCI), modulation of signal transduction, regulation of reactive oxygen species (ROS) production, etc. Though inositol pharmacology is a relatively lesser-known field, recent years of research has generated a critical mass of information on the subject. This review aims to summarize our current understanding on the role of inositol derivatives in ameliorating the symptoms of different diseases.

Risk of reduced intestinal absorption of myo-inositol caused by D-chiro-inositol or by glucose transporter inhibitors

ABSTRACTBackground: D-chiro-inositol (DCI) and glucose transporter inhibitors may inhibit myo-inositol (MI) transporters, and the aim is to clinically evaluate their effect on MI absorption.Research design and methods: Fasting 18 healthy volunteers received orally 6000 mg MI, 6000 mg MI with 1000 mg DCI, and 6000 mg MI with SelectSIEVE® Apple PCQ and Sorbitol, Maltodextrin and Sucralose (PCQ-SMS), in three different phases with a washout period of 7 days. At each phase, blood samples were collected before administration, and every 60 minutes until 540 minutes after administration. MI plasma levels (μmol/L) were quantified by gas chromatography-mass spectrometry; maximum plasma concentration (Cmax), time to reach it (Tmax), and the area under the time-concentration curve of MI (AUC 0-540) were evaluated.Results: The Cmax of MI alone (Tmax = 180min) was 1.29-fold higher than those of MI with DCI (Tmax = 180min) (p < 0.001) and 1.69-fold higher than those of MI with PCQ-SMS (Tmax = 240min) (p < 0.001). The AUC 0-540 was reduced by 19.09% in MI plus DCI (p = 0.0118) and by 31.8% in MI plus PCQ-SMS (p < 0.001) as compared to MI alone.Conclusions: DCI, glucose transporter inhibitors and sugars, such as sorbitol and maltodextrin, seem to inhibit MI absorption, decreasing MI plasma concentration as compared to MI alone.

The distribution of D-chiro-inositol in buckwheat and its antioxidative effect in HepG2

Epidemiological studies have shown that D-chiro-inositol (DCI) has multiple health effects in humans. Buckwheat, a nutritional staple crop, is a dietary source of DCI. We established a new economic method to accurately detect DCI content in buckwheat samples and investigated the antioxidant effect of DCI. In this study, we analyzed the content and form of DCI in buckwheat with different varieties, growth stages, and milled parts of seeds using pre-column derivatization and high performance liquid chromatography-ultraviolet detection. The total DCI content of ZK-2 and DT-1 was the highest. During buckwheat growth, DCI content was the highest in mature leaves. DCI was mainly in bound form in flowers and grains and mainly in free form in roots and stems. The highest content of DCI was 60–100-mesh in size in buckwheat grains. The results of cell experiments showed that DCI can inhibit the oxidative stress of HepG2 cells induced by palmitic acid (PA). This study will assist in the processing and utilization of buckwheat and provide an important basis for the scientific and effective use of D-chiro-inositol resources to increase the maximization of buckwheat resources.

D- chiro-Inositol Ameliorates High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance via PKCε-PI3K/AKT Pathway.

d- chiro-Inositol (DCI) is a biologically active component found in tartary buckwheat, which can reduce hyperglycemia and ameliorate insulin resistance. However, the mechanism underlying the antidiabetic effects of DCI remains largely unclear. This study investigated the effects and underlying molecular mechanisms of DCI on hepatic gluconeogenesis in mice fed a high fat diet and saturated palmitic acid-treated hepatocytes. DCI attenuated free fatty acid uptake by the liver via lipid trafficking inhibition, reduced diacylglycerol deposition, and hepatic PKCε translocation. Thus, DCI could improve insulin sensitivity by suppressing hepatic gluconeogenesis. Subsequent analyses revealed that DCI decreased hepatic glucose output and the expression levels of PEPCK and G6 Pase in insulin resistant mice through PKCε-IRS/PI3K/AKT signaling pathway. Likewise, such effects of DCI were confirmed in HepG2 cells with palmitate-induced insulin resistance. These findings indicate a novel pathway by which DCI prevents hepatic gluconeogenesis, reduces lipid deposition, and ameliorates insulin resistance via regulation of PKCε-PI3K/AKT axis.

Impact of Two Commercial Enzymes on the Release of Inositols, Fermentable Sugars, and Peptides in the Technology of Buckwheat Beer

The impact of two commercial enzyme preparations (Mats L Classic, Brewers Compass) used for mashing buckwheat malt was studied to assess their efficacies in releasing D-chiro- and myo-inositols, fermentable sugars and low molecular weight proteins and peptides. Concentrations of these compounds were determined in buckwheat malt, wort, and beer using sensitive ion-exchange and size exclusion chromatography techniques. These were preliminary studies whose general aim was to research the possibilities of functional beer production that could be dedicated for patients with coeliac disease. The application of enzyme preparations had no significant (Brewers Compass) or only little impact (Mats L Classic) on the recovery of D-chiro-inositol (DCI) and myo-inositol (MI) present in the buckwheat malt. In contrast to DCI, whose concentration in the buckwheat beer was 0.3 mg/mL, a minor fraction of MI (11–14.8%) was released into the beverage. In comparison to a barley beer, the oligosaccharide profile of the buckwheat beer was characterized by a relatively high proportion of residual sugars with a degree of polymerization above 5. SEC–HPLC chromatography showed significant changes within the polypeptide fractions after mashing and malting, with a marked increase in the proportion of low molecular weight peptides.

Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial

The purpose of this study was to evaluate the effect of two doses of D-chiro-inositol (DCI) in combination with Myo-inositol (MYO) in women with PCOS undergoing ICSI. This was a multicenter controlled, randomized, double-blind parallel group study with two MYO-DCI formulations for 12 weeks. The study group (SG) was administered 550 mg of MYO + 150 mg of DCI twice daily; the control group (CG) was administered 550 mg of MYO + 13.8 mg of DCI twice daily. The participants comprised 60 women with PCOS undergoing ICSI. At baseline, no differences were found between the two groups regarding age, BMI, HOMA-IR or testosterone levels. The pregnancy and live birth rates were significantly higher in the SG than in the CG (65.5 vs. 25.9 and 55.2 vs. 14.8, respectively) [risk ratio (RR) = 0.4; 95%CI (0.2, 0.79); p = .003 and RR = 0.27; 95%CI (0.10, 0.70); p = .002 respectively]. The risk of ovarian hyperstimulation syndrome (OHSS) was lower in the SG (3.44 vs. 18.5%, p = .07). The combination of MYO-DCI at high doses of DCI improves the pregnancy rates and reduces the risk of OHSS in women with PCOS undergoing ICSI.

There is no black hole swallowing water in the Hula Valley

The ratio of myo-inositol (MI) to d-chiro-inositol (DCI) seems to regulate the steroidogenesis in recruited follicles. While MI favors the increase of estrogens, DCI contributes to an androgenic environment, either by stimulating the biosynthesis of testosterone or by reducing its conversion to estradiol. Based on available evidence, we put forward the hypothesis that the different MI:DCI ratios influence the selection process, determining the dominant follicle and the follicles that will undergo atresia. We also suggest that the MI:DCI ratio may be regulated by follicles’ intrinsic characteristics, which possibly drive the cohort recruitment at each ovarian cycle.

Bioaccessibility of D-chiro-inositol from water biscuits formulated from buckwheat flours fermented by lactic acid bacteria and fungi

In this study, the bioaccessibility of D-chiro-inositol (DCI) from water biscuits formulated from raw and roasted buckwheat flours originating from common buckwheat after liquid-state fermentation (LSF) by select lactic acid bacteria (LAB) and fungi Rhizopus oligosporus 2740 was studied. The LAB-dependent variation in DCI content in fermented buckwheat flours was noted. LSF by L. salivarius AWH and R. oligosporus 2740 significantly enhanced the DCI content, whereas most of the applied LAB reduced DCI in the fermented flours. Baking at 220 °C for 30 min significantly enhanced the DCI level; however, no correlation was found between the DCI content in fermented flours and the biscuits prepared from them. The potential bioaccessibility of DCI from water biscuits was low. It can be concluded that, by applying select LAB and R. oligosporus 2740 for LSF, the heat treatment and physical structure of biscuits were mainly responsible for the potential bioaccessibility of DCI.

Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS).

To evaluate the effects of a combined Myo-inositol (MI) and D-chiro-inositol (DCI) therapy on the hormonal and metabolic parameters of women with PCOS. Prospective clinical study. Clinical Study registration number - EUPAS25705 Material and methods: Seventy women diagnosed with PCOS according to the Rotterdam criteria were enrolled in this study. Patients received a combined therapy of one tablet that contained 550 mg of inositol (myo-inositol (MI) and D-chiro-inositol (DCI) in a ratio of 10:1) twice a day for 6 months. At each of 3 visits, the body weight, height and BMI were all recorded; and serum levels of free testosterone (fT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and glucose with insulin during standard OGTT (75 g) were measured. Also at each visit, transvaginal ultrasonography and skin condition assessments were performed. Significant body weight reduction and decreases in fT, FSH, LH and insulin levels, as well as significant increase of serum SHBG concentrations were observed. Serum glucose levels during OGTT decreased after 6 months of treatment. Also, skin conditions improved after only three months of treatment. Combination of MI and DCI in a ratio 10:1 seems to be efficient in improving both metabolic and hormonal parameters in patients with PCOS.

Treatment with d-chiro-inositol and alpha lipoic acid in the management of polycystic ovary syndrome

To evaluate the effects of the combination of d-chiro inositol and alpha lipoic acid on menstrual cycles and insulin sensitivity in women with polycystic ovary syndrome (PCOS). Forty-one women with PCOS and 31 controls have been enrolled in the study. The menstrual cycle, BMI, homeostasis model assessment index (HOMA-I), and insulin secretion in response to an OGTT were evaluated before and after 6 months of treatment. During the observation period, the patients have been asked to not modify their diet and physical activity. The menstrual cycle length improved in 76.7% of the women. Ovulation was restored in 40%. During treatment, BMI significantly decreased (p<.002). The HOMA-I and insulin secretion were unchanged by treatment. However, when women were divided according to the presence of insulin resistance (IR; HOMA-I > 2.5), in those with IR the HOMA-I and the insulin secretion significantly decreased (p<.05 and p<.006). The association of d-chiro-inositol and alpha lipoic acid improves menstrual cycle length, restoring ovulation in the majority of women. Insulin sensitivity improved in women with IR only, confirming that in presence of IR the d-chiro-inositol has a role in restoring the insulin action overcoming the inactivity of epimerase in transforming myo-inositol to d-chiro inositol.

Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials.

Inositol (ISL) embraces a family of simple carbohydrates with insulin-sensitizing properties, whose most common isoforms are Myo-inositol (MYO) and D-chiro inositol (DCI). The aim of the present study was to assess the efficacy and safety of ISL supplementation during pregnancy for the prevention of gestational diabetes (GDM). We conducted a systematic literature search in electronic databases until October 2017. We included all randomized controlled trials (RCTs) comparing pregnant women with GDM who were randomized to either ISL (i.e., intervention group) or either placebo or no treatment (i.e., control group). The primary outcome was the preventive effect on GDM, defined as the rate of GDM in women without a prior diagnosis of GDM. Pooled results were expressed as odds ratio (OR) with a 95% confidence interval (95% CI). Five RCTs were included (including 965 participants). ISL supplementation was associated with lower rate of GDM (OR 0.49, 95% CI 0.24-1.03, p = 0.01) and lower preterm delivery rate (OR 0.35, 95% CI 0.17-0.74, p = 0.006). No adverse effects were reported. Adjusting for the type of intervention (MYO 2g twice daily vs MYO 1100mg plus DCI 27.6mg daily), a significant effect was found only in patients receiving 2g MYO twice daily. ISLs administration during pregnancy appears to be safe and may represent a novel strategy for GDM prevention. In particular, the double administration of MYO 2g per day may improve the glycemic homeostasis and may reduce GDM rate and preterm delivery rate.

The influence of different inositol stereoisomers supplementation in pregnancy on maternal gestational diabetes mellitus and fetal outcomes in high-risk patients: a randomized controlled trial

Objective: To identify the effects of different dietary inositol stereoisomers on insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk for this disorder.Design: A preliminary, prospective, randomized, placebo controlled clinical trial.Participants: Nonobese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy.Intervention: Supplementation with myo-inositol, d-chiro-inositol, combined myo- and d-chiro-inositol or placebo.Main outcome measure: Development of GDM on a 75 grams oral glucose tolerance test at 24–28 weeks’ gestation. Secondary outcome measures were increase in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia.Results: The group of women allocated to receive myo-inositol alone had a lower incidence of abnormal oral glucose tolerance test (OGTT). Nine women in the control group (C), one of the myo-inositol (MI), five in d-chiro-inositol (DCI), three in the myo-inositol/D-chiro-inositol group (MI/DCI) required insulin (p = .134). Basal, 1-hour, and 2 hours glycemic controls were significantly lower in exposed groups (p < .001, .011, and .037, respectively). The relative risk reduction related to primary outcome was 0.083, 0.559, and 0.621 for MI, DCI, and MI/DCI groups.Conclusions: This study compared the different inositol stereoisomers in pregnancy to prevent GDM. Noninferiority analysis demonstrated the largest benefit in the myo-inositol group. The relevance of our findings is mainly related to the possibility of an effective approach in GDM. Our study confirmed the efficacy of inositol supplementation in pregnant women at risk for GDM.

Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol

d-chiroinositol (DCI) is a inositolphosphoglycan (IPG) involved in several cellular functions that control the glucose metabolism. DCI functions as second messenger in the insulin signaling pathway and it is considered an insulin sensitizer since deficiency in tissue availability of DCI were shown to cause insulin resistance (IR). Polycystic ovary syndrome (PCOS) is a pathological condition that is often accompanied with insulin resistance. DCI can positively affects several aspect of PCOS etiology decreasing the total and free testosterone, lowering blood pressure, improving the glucose metabolism and increasing the ovulation frequency. The purpose of this study was to evaluate the effects of DCI and insulin combined with gonadotrophins namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on key steroidogenic enzymes genes regulation, cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and cytochrome P450 side-chain cleavage (P450scc) in primary cultures of human granulosa cells (hGCs). We also investigated whether DCI, being an insulin-sensitizer would be able to counteract the expected stimulator activity of insulin on human granulosa cells (hGCs). Methods. The study was conducted on primary cultures of hGCs. Gene expression was evaluated by RT-qPCR method. Statistical analysis was performed applying student t-test, as appropriate (P < 0.05) set for statistical significance. Results. DCI is able to reduce the gene expression of CYP19A1, P450scc and insulin-like growth factor 1 receptor (IGF-1R) in dose–response manner. The presence of DCI impaired the increased expression of steroidogenic enzyme genes generated by the insulin treatment in gonadotrophin-stimulated hGCs. Conclusions. Insulin acts as co-gonadotrophin increasing the expression of steroidogenic enzymes genes in gonadotrophin-stimulated granulosa cells. DCI is an insulin-sensitizer that counteracts this action by reducing the expression of the genes CYP19A1, P450scc and IGF-1R. The ability of DCI to modulate in vitro ovarian activity of insulin could in part explain its beneficial effect when used as treatment for conditions associated to insulin resistance.

Vascular and metabolic profiles in offspring born to pregnant mice with metabolic syndrome treated with inositols

Inositols (INOs) supplementation during pregnancy, specifically the combination of myo-inositol (MI) and D-chiro-inositol (DCI), has been reported to improve vascular parameters in women with gestational diabetes mellitus. We demonstrated previously that offspring born to pregnant mice lacking the endothelial nitric oxide synthase (eNOS+/-) gene have hypertension (HTN) as adults and, when fed a high-fat diet (HFD), develop a metabolic syndrome (MS) phenotype. Our aim was to evaluate whether INOs treatment in pregnancy complicated by MS improves the vascular and metabolic profile in mice offspring programmed in utero to develop HTN and MS. Heterozygous eNOS+/- mice fed an HFD manifest a MS phenotype. Female eNOS+/- mice with MS were bred with a wild-type (WT) male. On gestational day 1, pregnant females were randomly allocated to receive either a mixture of INOs (MI/DCI: 7.2/0.18 mg/mL) or water as placebo until delivery. The female offspring obtained were genotyped and categorized as: WT (genetically normal, with eNOS gene) and eNOS+/- offspring (genetically modified, heterozygous for eNOS gene). Both offspring developed in an abnormal uterine environment due to maternal MS. At 9-10 weeks of age, the offspring underwent a glucose tolerance test (GTT) and systolic blood pressure (SBP) measurement. The mice were then sacrificed, and the carotid arteries were isolated for evaluation of vascular responses. Responses to phenylephrine (PE), in the presence and absence of a nonspecific nitric oxide inhibitor (N-nitro-L-arginine methyl ester [L-NAME]), the vasodilator acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed. The GTT showed lower glucose levels in both eNOS+/-INOs (P= .03) and WT-INOs (P= .05) offspring born to MS dams on INOs supplementation compared to offspring born to untreated dams. SBP was higher in eNOS+/- offspring compared to WT (169 ± 7 vs 142 ± 9 mm Hg, respectively, P= .04) and INOs treatment decreased SBP in WT-INOs (110 ± 10 mm Hg, P= .01) but not in eNOS+/-INOs offspring. Maximal (%Max) contractile response to PE was higher in eNOS+/- offspring born to MS dams and was decreased in those born to MS dams treated with INOs (%Max, eNOS+/-, 123 ± 7 vs eNOS+/-INOs, 82 ± 11 mm Hg, P= .007). No differences were seen in PE contractile responses in WT offspring born to MS dams treated or not treated with INOs (WT, 92 ± 4 vs WT-INOs, 75 ± 7). The L-NAME response was decreased in eNOS+/-INOs and WT-INOs offspring compared to untreated ones. The ACh vasorelaxation was impaired in eNOS+/- and WT offspring born to MS dams, and maternal INOs treatment improved offspring vascular relaxation in both offspring (P= .01 and P= .03, respectively). No differences were seen in response to SNP. Inositols supplementation improved glucose tolerance, SBP, and vascular responses in adult eNOS+/- and WT offspring born to dams with MS. Interestingly, WT born to MS dams show an altered vascular profile similar to eNOS+/- offspring and exhibit an improved response to INOs treatment. Our findings suggest that the benefits of INOs treatment are more pronounced in offspring exposed to environmental factors in utero, and less likely in those due to genetic factors.

The analysis of fagopyritols from tartary buckwheat and their anti-diabetic effects in KK-Ay type 2 diabetic mice and HepG2 cells

The studies of fagopyritols in tartary buckwheat and their anti-diabetic effects are limited. The fagopyritol B1 was the major fagopyritol in tartary buckwheat. The content of fagopyritols was 11-fold of free D-chiro-inositol (DCI) in tartary buckwheat. In KK-Ay mice, administration of fagopyritol B1 for 6-week was more effective in suppressing progressive rise of blood glucose, improving impaired glucose tolerance, and increasing insulin sensitivity than DCI and fagopyritol A1. Besides, both of fagopyritols and DCI improved the lipid homeostasis. Fagopyritols increased the expression of insulin receptor and PI3K in liver and skeletal muscle, as the same as DCI. According to the in vitro study, fagopyritols and DCI increased glucose consumption in both normal and insulin resistant HepG2 cells. In addition, fagopyritols and DCI upregulated phosphorylation of PI3K and AKT. In summary, these findings suggested that fagopyritols and DCI have potential anti-diabetic effects via activation of the insulin dependent pathway of PI3K/AKT.

Myo-inositol supplementation reduces the amount of gonadotropins and length of ovarian stimulation in women undergoing IVF: a systematic review and meta-analysis of randomized controlled trials.

To evaluate whether oral myo-inositol supplementation (MI) is able to reduce the amount of gonadotropins (GA) and the length of controlled ovarian hyperstimulation (SL) in both Polycystic Ovarian Syndrome (PCOS) and non-PCOS women undergoing in vitro fertilization (IVF). We performed a systematic review (PROSPERO ID: CRD42017069439) of randomized controlled trials (RCTs). We searched articles published in English between January 1985 to August 2017, using the combination of the Medical Subject Headings "Inositol" with "Ovulation Induction", "follicle-stimulating hormone, human, with HCG C-terminal peptide", "Reproductive Techniques, Assisted", and "Fertilization in Vitro". We collected data about GA and SL comparing MI to no treatment or D-Chiro-Inositol (DCI) supplementation (controls). A subgroup analysis was performed to evaluate selected outcomes in PCOS and non-PCOS women. We included 8 studies embedding 812 participants. We found a reduction in GA (p < 0.00001) and SL (p = 0.0007) in patients receiving MI with respect to controls. MI was effective in both PCOS (p < 0.00001) and non-PCOS women (p = 0.02) in reducing GA; conversely, MI supplementation decreased the SL only in PCOS women (p < 0.00001). During IVF, MI is effective in both PCOS and non-PCOS women in saving gonadotropins, but reduces efficiently SL only in PCOS women.