Highly enhanced removal of Cr(VI) by nZVI in presence of myo-inositol hexakisphosphate: The depassivation performance and multiple electron transfer mechanisms.

The capability of traditional ligand in countering rapid passivation on nanoscale zero-valent iron (nZVI) surface is inadequate, and the precise electron transfer mechanism remains elusive. In this study, we reported that myo-inositol hexakisphosphate (IHP), a redox-inactive organophosphorus in soil, could highly enhance Cr(VI) reduction and immobilization in comparison with typical ligands (TPP, EDTA, oxalate and phosphate). And the effects of IHP concentration, Cr(VI) concentration and initial pH were systematically investigated. Cr K-edge XANES and XPS analysis revealed that Cr(III) was the exclusive form in solid products regardless of IHP existence. Results of ATR-FTIR and FESEM inferred that IHP was adsorbed on nZVI surface via inner-sphere complexation, thus averting encapsulation of [Fe, Cr](OH)3 coprecipitate and impeding solid particles agglomeration. Additionally, IHP expedited the production of surface-bound Fe(II), primarily attributable to the interaction between nZVI and oxygen. These surface-bound Fe(II) species played a pivotal role in Cr(VI) reduction. Electrochemical analysis unveiled that IHP lowered redox potential of Fe(III)/Fe(II), thereby facilitating reaction between Fe(II) and Cr(VI), whereas inhibited direct electron transfer from nZVI core to Cr(VI). Our findings proposed a novel potential ligand for alleviating nZVI passivation in Cr(VI) removal and deepened our understanding in the process of electron transfer.

African swine fever virus modulates the endoplasmic reticulum stress-ATF6-calcium axis to facilitate viral replication.

African swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating infectious disease of domestic pigs and wild boar, which threatens the global pig industry. Endoplasmic reticulum (ER) is a multifunctional signaling organelle in eukaryotic cells that is involved in protein synthesis, processing, posttranslational modification and quality control. As intracellular parasitic organisms, viruses have evolved several strategies to modulate ER functions to favor their life cycles. We have previously demonstrated that the differentially expressed genes associated with unfolded protein response (UPR), which represents a response to ER stress, are significantly enriched upon ASFV infection. However, the correlation between the ER stress or UPR and ASFV replication has not been illuminated yet. Here, we demonstrated that ASFV infection induces ER stress both in target cells and in vivo, and subsequently activates the activating transcription factor 6 (ATF6) branch of the UPR to facilitate viral replication. Mechanistically, ASFV infection disrupts intracellular calcium (Ca2+) homeostasis, while the ATF6 pathway facilitates ASFV replication by increasing the cytoplasmic Ca2+ level. More specifically, we demonstrated that ASFV infection triggers ER-dependent Ca2+ release via the inositol triphosphate receptor (IP3R) channel. Notably, we showed that the ASFV B117L protein plays crucial roles in ER stress and the downstream activation of the ATF6 branch, as well as the disruption of Ca2+ homeostasis. Taken together, our findings reveal for the first time that ASFV modulates the ER stress-ATF6-Ca2+ axis to facilitate viral replication, which provides novel insights into the development of antiviral strategies for ASFV.

Comparison of metformin with inositol versus metformin alone in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Metformin was the first medication targeting insulin resistance in PCOS, and it has been extensively studied as a metabolic treatment option. In recent years, inositols have emerged as potential treatment options for PCOS, but confidence in the available evidence supporting their use is limited. METHODS: We comprehensively searched PubMed, Embase, and Cochrane databases for RCTs comparing the use of combined metformin and inositol versus metformin alone in women with PCOS. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). A p-value of <0.05 was deemed as statistically significant. RESULTS: Six RCTs and 388 patients were included in the analysis, with follow-up ranging from 3 to 6 months. Combination therapy was significantly associated with improved menstrual cycle regularity (RR 1.56; 95% CI 1.01 to 2.41; p = 0.04), and lower values of modified Ferriman-Gallwey score (MD -0.97; 95% CI -1.53 to -0.40; p < 0.01) and LH/FSH ratios (MD -0.13; 95% CI -0.24 to -0.03; p = 0.01). Differences in acne (p = 0.58), body mass index (p = 0.13), fasting blood glucose (p = 0.07) and HOMA-IR (p = 0.25) were not statistically significant. CONCLUSION: In this meta-analysis of RCTs, combination therapy was associated with cycle regularization and reduction in hirsutism and LH/FSH ratio compared to metformin monotherapy. Further studies are needed to clarify the true benefits of the use of inositol in PCOS treatment.

Bacillus subtilis grown in a "breathing" vessel without sparger aeration.

Here we present a "breathing" vessel consisting of expanded polytetrafluoroethylene, which allows gas exchange but no liquid permeation. The bacterial culture inside needs only agitation to promote air supply. Using this setup, a Bacillus subtilis cell factory for scyllo-inositol production grew to produce scyllo-inositol efficiently. The results indicate that our approach represents a sustainable "greener" approach for the cell factory.

Mechanism of Stimulation of Myogenesis under the Action of Succinic Acid through the Succinate Receptor SUCNR1.

Effect of succinic acid on the processes of myogenesis was investigated in the study with the cells of C2C12 line. In the concentration range 10-1000 µM, succinic acid stimulated the process of myogenic differentiation, increasing the levels of myogenesis factors MyoD (at all stages of myogenesis) and myogenin (at the stage of terminal differentiation). Presence of the succinate receptors SUCNR1 was revealed in the C2C12 cells using Western blotting, level of which decreased during myogenesis. When succinic acid was added to the cells, the level of intracellular succinate did not change significantly and decreased during myogenic differentiation. Using a specific Gai protein inhibitor, pertussis toxin, it was found that stimulation of myogenesis in the C2C12 cells under the action of succinic acid is realized through SUCNR1-Gai interaction.

Pharmacological management of polycystic ovary syndrome.

Polycystic ovary syndrome is a common and frequently undiagnosed female endocrine disorder that is associated with diverse symptoms and features, and an increased risk of long-term chronic diseases such as type 2 diabetes and cardiovascular disease. Pharmacotherapy for polycystic ovary syndrome should be directed at the key concerns of the individual patient. The combined oral contraceptive pill or metformin may be prescribed for irregular periods. The combined oral contraceptive pill is preferred over antiandrogens for treatment of hirsutism and acne. Metformin is of benefit for reducing excess body weight and improving hormonal and metabolic outcomes in those with high metabolic risk (e.g. body mass index greater than 25 kg/m2). Inositol appears to have limited benefits for metabolic outcomes, although it is associated with fewer adverse effects than metformin. Modification of lifestyle factors is important as part of a holistic approach to managing polycystic ovary syndrome. Anti-obesity drugs may be considered for weight management in addition to lifestyle interventions.

Interaction with IP6K1 supports pyrophosphorylation of substrate proteins by the inositol pyrophosphate 5-InsP7.

Inositol pyrophosphates (PP-InsPs) are a sub-family of water soluble inositol phosphates that possess one or more diphosphate groups. PP-InsPs can transfer their ß-phosphate group to a phosphorylated Ser residue to generate pyrophosphorylated Ser. This unique post-translational modification occurs on Ser residues that lie in acidic stretches within an intrinsically disordered protein sequence. Serine pyrophosphorylation is dependent on the presence of Mg2+ ions, but does not require an enzyme for catalysis. The mechanisms by which cells regulate PP-InsP-mediated pyrophosphorylation are still unknown. We performed mass spectrometry to identify interactors of IP6K1, an enzyme responsible for the synthesis of the PP-InsP 5-InsP7. Interestingly, IP6K1 interacted with several proteins that are known to undergo 5-InsP7-mediated pyrophosphorylation, including the nucleolar proteins NOLC1, TCOF and UBF1, and AP3B1, the ß subunit of the AP3 adaptor protein complex. The IP6K1 interactome also included CK2, a protein kinase that phosphorylates Ser residues prior to pyrophosphorylation. We observe the formation of a protein complex between IP6K1, AP3B1, and the catalytic α-subunit of CK2, and show that disrupting IP6K1 binding to AP3B1 lowers its in vivo pyrophosphorylation. We propose that assembly of a substrate-CK2-IP6K complex would allow for coordinated pre-phosphorylation and pyrophosphorylation of the target serine residue, and provide a mechanism to regulate this enzyme-independent modification.

Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.

Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac dysfunction which precede HF are not well-defined. Among older individuals without HF in the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of 47 circulating metabolites measured by 1H-NMR with echocardiographic measures of cardiac structure and function. We then evaluated associations of significant metabolites with circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a separate cohort, we evaluated differences between top metabolites in patients with HF with preserved ejection fraction (HFpEF) and comorbidity-matched controls. Genetic variants associated with top metabolites (mQTLs) were then related to echocardiographic measures and NT-proBNP. Among 3440 individuals with metabolic and echocardiographic data in MESA (62 ± 10 years, 52% female, 38% White), 10 metabolites broadly reflective of glucose and amino acid metabolism were associated with at least 1 measure of cardiac structure or function. Of these 10 metabolites, 4 (myo-inositol, glucose, dimethylsulfone, carnitine) were associated with higher NT-proBNP and 2 (d-mannose, acetone) were associated with lower NT-proBNP. In a separate cohort, patients with HFpEF had higher circulating myo-inositol levels compared with comorbidity-matched controls. Genetic analyses revealed that 1 of 6 known myo-inositol mQTLs conferred risk of higher NT-proBNP. In conclusion, metabolomic profiling identifies several novel metabolites associated with cardiac dysfunction in a cohort at high risk for HF, revealing pathways potentially relevant to future HF risk.

High Impact AMPAkines Induce a Gq-Protein Coupled Endoplasmic Calcium Release in Cortical Neurons: A Possible Mechanism for Explaining the Toxicity of High Impact AMPAkines.

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) positive allosteric modulators (AMPAkines) have a multitude of promising therapeutic properties. The pharmaceutical development of high impact AMPAkines has, however, been limited by the appearance of calcium-dependent neuronal toxicity and convulsions in vivo. Such toxicity is not observed at exceptionally high concentrations of low impact AMPAkines. Because most AMPAR are somewhat impermeable to calcium, the current study sought to examine the extent to which different mechanisms contribute to the rise in intracellular calcium in the presence of high impact ampakines. In the presence of AMPA alone, cytosolic calcium elevation is shown to be sodium-dependent. In the presence of high impact AMPAkines such as cyclothiazide (CTZ) or CX614, however, AMPAR potentiation also activates an additional mechanism that induces calcium release from endoplasmic reticular (ER) stores. The pathway that connects AMPAR to the ER system involves a Gq-protein, phospholipase Cß-mediated inositol triphosphate (InsP3) formation, and ultimately stimulation of InsP3-receptors located on the ER. The same linkage was not observed using high concentrations of the low impact AMPAkines, CX516 (Ampalex), and CX717. We also demonstrate that CX614 produces neuronal hyper-excitability at therapeutic doses, whereas the newer generation low impact AMPAkine CX1739 is safe at exceedingly high doses. Although earlier studies have demonstrated a functional linkage between AMPAR and G-proteins, this report demonstrates that in the presence of high impact AMPAkines, AMPAR also couple to a Gq-protein, which triggers a secondary calcium release from the ER and provides insight into the disparate actions of high and low impact AMPAkines.

Characterization and comparison of metabolites in colostrum from yaks, buffaloes, and cows based on UPLC-QTRAP-MS metabolomics.

Colostrum from yaks and buffaloes possesses substantial nutritional value, yet the complete array of metabolites within remains insufficiently elucidated. This study scrutinizes the metabolite profiles of yak, buffalo, and cow colostrum utilizing targeted metabolomics paired with ultra-performance liquid chromatography-tandem triple quadrupole linear ion trap mass spectrometry (UPLC-QTRAP-MS). The analysis detected 362 metabolites across all samples. Furthermore, 63, 77, and 46 differential metabolites were selected between yak and buffalo colostrum, yak and cow colostrum, and buffalo and cow colostrum, respectively. Yak colostrum notably contained higher concentrations of inositol, glycine, and carnitine, whereas buffalo colostrum was distinguished by a substantial presence of primary bile acids, which facilitate fat digestion. These findings offer profound insights into yak and buffalo colostrum, providing critical data to propel advancements in the dairy industry.

KRN5b regulates maize kernel row number through mediating phosphoinositol signalling.

Kernel row number (KRN) is a major yield related trait for maize (Zea mays L.) and is also a major goal of breeders, as it can increase the number of kernels per plant. Thus, identifying new genetic factors involving in KRN formation may accelerate improving yield-related traits genetically. We herein describe a new kernel number-related gene (KRN5b) identified from KRN QTL qKRN5b and encoding an inositol polyphosphate 5-phosphatase (5PTase). KRN5b has phosphatase activity towards PI(4,5)P2, PI(3,4,5)P3, and Ins(1,4,5)P3 in vitro. Knocking out KRN5b caused accumulation of PI(4,5)P2 and Ins(1,4,5)P3, resulting in disordered kernel rows and a decrease in the number of kernels and tassel branches. The introgression of the allele with higher expression abundance into different inbred lines could increase the ear weight of the inbred lines and the corresponding hybrids by 10.1%-12.2% via increasing KRN, with no adverse effects on other agronomic traits. Further analyses showed that KRN5b regulates inflorescence development through affecting the synthesis and distribution of hormones. Together, KRN5b contributes to spikelet pair meristem development through inositol phosphate and phosphatidylinositols, making it a selecting target for yield improvement.

Inositol Hexaphosphate in Bone Health and Disease.

Dietary phytic acid/phytate/myo-inositol hexaphosphate (IP6), a phosphate reservoir in plants, was viewed as antinutrient, caused by an influence on the bioavailability of minerals through its chelating activity. However, there is a growing body of evidence indicating that IP6 has beneficial (e.g., antiinflammatory, antibacterial, and anticancer) effects on multiple biological processes. Also, IP6 and its metabolites are known to exist in mammalian cells, including human cells, and the role of IP6 as a functional molecule is attracting attention. IP6 can bind to the growth sites of hydroxy-apatite (HA) and calcium oxalate crystals to prevent their growth and hence inhibit pathological calcification. SNF472, hexasodium IP6, is currently being evaluated in clinical studies as a treatment for vascular calcification and calciphylaxis. However, since HA crystal growth within bone matrix is an essential process in bone formation, it is possible that IP6 intake may inhibit physiological mineralization and bone formation, although currently more published studies suggest that IP6 may contribute to bone health rather than inhibit bone formation. Given that IP6 and its metabolites are thought to have diverse activities and many health benefits, it remains important to consider the range of effects of IP6 on bone.

Encapsulation of Inositol Hexakisphosphate with Chitosan via Gelation to Facilitate Cellular Delivery and Programmed Cell Death in Human Breast Cancer Cells.

Inositol hexakisphosphate (InsP6) is the most abundant inositol polyphosphate both in plant and animal cells. Exogenous InsP6 is known to inhibit cell proliferation and induce apoptosis in cancerous cells. However, cellular entry of exogenous InsP6 is hindered due to the presence of highly negative charge on this molecule. Therefore, to enhance the cellular delivery of InsP6 in cancerous cells, InsP6 was encapsulated by chitosan (CS), a natural polysaccharide, via the ionic gelation method. Our hypothesis is that encapsulated InsP6 will enter the cell more efficiently to trigger its apoptotic effects. The incorporation of InsP6 into CS was optimized by varying the ratios of the two and confirmed by InsP6 analysis via polyacrylamide gel electrophoresis (PAGE) and atomic absorption spectrophotometry (AAS). The complex was further characterized by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR) for physicochemical changes. The data indicated morphological changes and changes in the spectral properties of the complex upon encapsulation. The encapsulated InsP6 enters human breast cancer MCF-7 cells more efficiently than free InsP6 and triggers apoptosis via a mechanism involving the production of reactive oxygen species (ROS). This work has potential for developing cancer therapeutic applications utilizing natural compounds that are likely to overcome the severe toxic effects associated with synthetic chemotherapeutic drugs.

Efficient Improvement of Eugenol Water Solubility by Spray Drying Encapsulation in Soluplus® and Lutrol F 127.

Herein, we present an elegant and simple method for significant improvement of eugenol water solubility using the polymers Soluplus® and Lutrol F 127 as carriers and spray drying as an encapsulation method. The formulations were optimized by adding myo-inositol-a sweetening agent-and Aerosil® 200 (colloidal, fumed silica)-an anticaking agent. The highest encapsulation efficiency of 97.9-98.2% was found for the samples containing 5% eugenol with respect to the mass of Soluplus®. The encapsulation efficiencies of the spray-dried samples with 15% eugenol are around 90%. Although lowering the yield, the addition of Lutrol F 127 results in a more regular particle shape and enhanced powder flowability. The presence of Aerosil® 200 and myo-inositol also improves the rheological powder properties. The obtained formulations can be used in various dosage forms like powders, granules, capsules, creams, and gels.

Activation of IP3R in atrial cardiomyocytes leads to generation of cytosolic cAMP.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Excessive stimulation of the inositol (1,4,5)-trisphosphate (IP3) signaling pathway has been linked to AF through abnormal calcium handling. However, little is known about the mechanisms involved in this process. We expressed the fluorescence resonance energy transfer (FRET)-based cytosolic cyclic adenosine monophosphate (cAMP) sensor EPAC-SH187 in neonatal rat atrial myocytes (NRAMs) and neonatal rat ventricular myocytes (NRVMs). In NRAMs, the addition of the α1-agonist, phenylephrine (PE, 3 µM), resulted in a FRET change of 21.20 ± 7.43%, and the addition of membrane-permeant IP3 derivative 2,3,6-tri-O-butyryl-myo-IP3(1,4,5)-hexakis(acetoxymethyl)ester (IP3-AM, 20 µM) resulted in a peak of 20.31 ± 6.74%. These FRET changes imply an increase in cAMP. Prior application of IP3 receptor (IP3R) inhibitors 2-aminoethyl diphenylborinate (2-APB, 2.5 µM) or Xestospongin-C (0.3 µM) significantly inhibited the change in FRET in NRAMs in response to PE. Xestospongin-C (0.3 µM) significantly inhibited the change in FRET in NRAMs in response to IP3-AM. The FRET change in response to PE in NRVMs was not inhibited by 2-APB or Xestospongin-C. Finally, the localization of cAMP signals was tested by expressing the FRET-based cAMP sensor, AKAP79-CUTie, which targets the intracellular surface of the plasmalemma. We found in NRAMs that PE led to FRET change corresponding to an increase in cAMP that was inhibited by 2-APB and Xestospongin-C. These data support further investigation of the proarrhythmic nature and components of IP3-induced cAMP signaling to identify potential pharmacological targets.NEW & NOTEWORTHY This study shows that indirect activation of the IP3 pathway in atrial myocytes using phenylephrine and direct activation using IP3-AM leads to an increase in cAMP and is in part localized to the cell membrane. These changes can be pharmacologically inhibited using IP3R inhibitors. However, the cAMP rise in ventricular myocytes is independent of IP3R calcium release. Our data support further investigation into the proarrhythmic nature of IP3-induced cAMP signaling.

Oral supplementation of inositols effectively recovered lithium-induced cardiac dysfunctions in mice.

This study investigates the effects of inositol (INO) supplementation on cardiac changes caused by Li in mice. The study involved 4 groups of C57BL6 mice (n=10 each): (i) mice orally administered with Li2CO3 for 8 weeks, then 4 additional weeks without (Li_group) or (ii) with INO supplementation (Li_INOdelayed_group) (total of 12 weeks); (iii) mice given Li2CO3 and INO supplementation concurrently for 12 weeks (Li+INO_group); (iv) one group left untreated (C-group). The INO was administered as a mixture of myo-inositol and d-chiro-inositol (80:1) in drinking water. The mice were characterised for heart morphology, function, electrical activity, arrhythmogenic susceptibility, and multiorgan histopathology (heart, liver and kidney). Cardiomyocyte size, protein expression of key signalling pathways related to hypertrophy, and transcription levels of ion channel subunits and hypertrophy markers were evaluated in the ventricle tissue. The study found that INO supplementation reduced the Li-induced cardiac adverse effects, including systolic impairment and increased susceptibility to arrhythmias. The positive effect on arrhythmias might be attributed to the restored expression levels of the potassium channel subunit Kv 1.5. Additionally, INO improved cardiomyocyte hypertrophy, possibly by inhibiting the Li-induced activation of the ERK1/2 signalling pathway and by restoring the normal expression level of BNP, and alleviated injury in the liver and kidney. The effect was preventive if INO supplementation was taken concurrently with Li and therapeutic if INO was administered after Li-induced cardiac impairments were established. These results provide new insights into the cardioprotective effect of INO and suggest a potential treatment approach for Li-induced cardiac disease.

Correlation between tooth decay and insulin resistance in normal weight males prompts a role for myo-inositol as a regenerative factor in dentistry and oral surgery: a feasibility study.

Background: In an era of precision and stratified medicine, homogeneity in population-based cohorts, stringent causative entry, and pattern analysis of datasets are key elements to investigate medical treatments. Adhering to these principles, we collected in vivo and in vitro data pointing to an insulin-sensitizing/insulin-mimetic effect of myo-inositol (MYO) relevant to cell regeneration in dentistry and oral surgery. Confirmation of this possibility was obtained by in silico analysis of the relation between in vivo and in vitro results (the so-called bed-to-benchside reverse translational approach). Results: Fourteen subjects over the 266 screened were young adult, normal weight, euglycemic, sedentary males having normal appetite, free diet, with a regular three-times-a-day eating schedule, standard dental hygiene, and negligible malocclusion/enamel defects. Occlusal caries were detected by fluorescence videoscanning, whereas body composition and energy balance were estimated with plicometry, predictive equations, and handgrip. Statistically significant correlations (Pearson r coefficient) were found between the number of occlusal caries and anthropometric indexes predicting insulin resistance (IR) in relation to the abdominal/visceral fat mass, fat-free mass, muscular strength, and energy expenditure adjusted to the fat and muscle stores. This indicated a role for IR in affecting dentin reparative processes. Consistently, in vitro administration of MYO to HUVEC and Swiss NIH3T3 cells in concentrations corresponding to those administered in vivo to reduce IR resulted in statistically significant cell replication (ANOVA/Turkey tests), suggesting that MYO has the potential to counteract inhibitory effects of IR on dental vascular and stromal cells turnover. Finally, in in silico experiments, quantitative evaluation (WOE and information value) of a bioinformatic Clinical Outcome Pathway confirmed that in vitro trophic effects of MYO could be transferred in vivo with high predictability, providing robust credence of its efficacy for oral health. Conclusion: Our reverse bed-to-benchside data indicate that MYO might antagonize the detrimental effects of IR on tooth decay. This provides feasibility for clinical studies on MYO as a regenerative factor in dentistry and oral surgery, including dysmetabolic/aging conditions, bone reconstruction in oral destructive/necrotic disorders, dental implants, and for empowering the efficacy of a number of tissue engineering methodologies in dentistry and oral surgery.

Influence of myo-inositol on metabolic status for gestational diabetes: a meta-analysis of randomized controlled trials.

INTRODUCTION: The efficacy of myo-inositol supplementation to treat gestational diabetes remains controversial, and this meta-analysis aims to study the efficacy of myo-inositol supplementation on metabolic status for gestational diabetes. METHODS: Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systemically searched from inception to October 2021, and we included the randomized controlled trials (RCTs) assessing the effect of myo-inositol supplementation on the outcomes of women with gestational diabetes. Gestational diabetes was diagnosed if at least one threshold of glucose concentration was exceeded and the three thresholds included 92, 180, and 153 mg/dl for 0, 1 and 2 h, respectively, after a 75-g, 2-h glucose tolerance test. RESULTS: Four RCTs and 317 patients were included in this meta-analysis. Compared with routine treatment in pregnant women with gestational diabetes, myo-inositol supplementation could lead to remarkably decreased treatment requirement with insulin (odd ratio [OR] = 0.24; 95% confidence interval [CI] = 0.11-0.52; p = .0003) and homeostasis model assessment of insulin resistance (HOMA-IR, standard mean difference [SMD]= -1.18; 95% CI= -1.50 to -0.87; p < .00001), but demonstrated no obvious impact on birth weight (SMD= -0.11; 95% CI= -0.83 to 0.61 g; p = .76), cesarean section (OR = 0.82; 95% CI = 0.46-1.47; p = .51) or the need of NICU (OR = 0.88; 95% CI = 0.03-26.57; p = .94). CONCLUSIONS: Myo-inositol supplementation is effective to decrease the need of insulin treatment and HOMA-IR for gestational diabetes.

Genetic Deletion of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Homeostasis and Impairs Exercise Tolerance.

Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways in which inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is still poorly understood. Since skeletal muscle is a major contributor to energy homeostasis, we have developed a mouse model in which skeletal muscle IPMK is specifically deleted and examined how a loss of IPMK affects whole-body metabolism. Here, we report that mice in which IPMK knockout is deleted, specifically in the skeletal muscle, displayed an increased body weight, disrupted glucose tolerance, and reduced exercise tolerance under the normal diet. Moreover, these changes were associated with an increased accumulation of triglyceride in skeletal muscle. Furthermore, we have confirmed that a loss of IPMK led to reduced beta-oxidation, increased triglyceride accumulation, and impaired insulin response in IPMK-deficient muscle cells. Thus, our results suggest that IPMK mediates the whole-body metabolism via regulating muscle metabolism and may be potentially targeted for the treatment of metabolic syndromes.

A rapid and validated GC-MS/MS method for simultaneous quantification of serum Myo- and D-chiro-inositol isomers.

BACKGROUND: Myo-inositol (MI) and D-chiro-inositol (DCI) are two paramount isomers of inositol, both vital in glucose and steroid metabolism. Deficits in MI, DCI or MI/DCI ratio are expressly concerned with several pathological process, whereas MI and DCI lack practical measurement for human specimen. METHODS: To quantify MI and DCI in serum samples simultaneously, a gas chromatography tandem mass spectrometry (GC-MS/MS) method was established. The process flow was optimized in ion source, derivative agent volume and reaction time. The performance characteristics were verified by commercial standards and clinical serums. RESULTS: This method was confirmed to be sensitive (LOD ≤ 30 ng/mL of MI, ≤3 ng/mL of DCI) and reproducible (RSD < 6 % for repeated analyses). Quantitative determinations performed good linearity within the measurement range of 0.500-10.00 and 0.005-0.500 µg/mL for MI and DCI respectively (R2 > 0.999). The recoveries of MI and DCI were 97.11-99.35 % and 107.82-113.09 %, respectively. This method was successfully applied to 114 clinical specimens. No significant matrix effect was observed in serum samples under current conditions.