Potential role and therapeutic interests of myo-inositol in metabolic diseases.
TL;DR: The aim of this review is to focus on the potential benefits of a dietary supplement of myo-inositol, by far the most common inositol isomer in foodstuffs, in human disorders associated with insulin resistance, in prevention or treatment of some diabetic complications (neuropathy, nephropathy, cataract), and the relevance of such a nutritional strategy for each context on the basis of the clinical and/or animal studies.
About: This article is published in Biochimie.The article was published on 2013-10-01. It has received 385 citations till now. The article focuses on the topics: Inositol monophosphatase & D-chiro-Inositol.
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TL;DR: Results show that multivariate statistical approach, based on 1H NMR metabolite profiling, is a powerful tool for detecting ongoing differences in VH composition and may be applied to investigate several physiological and pathological conditions.
Abstract: We applied a metabolomic approach to monitor the modifications occurring in goat vitreous humor (VH) metabolite composition at different times (0, 6, 12, 18, and 24 hours) after death. The 1H-NMR analysis of the VH samples was performed for the simultaneous determination of several metabolites (i.e., the metabolite profile) representative of the VH status at different times. Spectral data were analyzed by Principal Component Analysis (PCA) and by Orthogonal Projection to Latent Structures (OPLS) regression technique. PCA and OPLS suggested that different spectral regions were involved in time-related changes. The major time-related compositional changes, here detected, were the increase of lactate, hypoxanthine, alanine, total glutathione, choline/phosphocholine, creatine, and myo-inositol and the decrease of glucose and 3-hydroxybutyrate. We attempted a speculative interpretation of the biological mechanisms underlying these changes. These results show that multivariate statistical approach, based on 1H NMR metabolite profiling, is a powerful tool for detecting ongoing differences in VH composition and may be applied to investigate several physiological and pathological conditions.
214 citations
Cites background from "Potential role and therapeutic inte..."
...This can be the case of MI involved in osmoregulation [24, 25], which after 12 hours showed an increase that can be explained by passive diffusion— through a concentration gradient determined by the uneven molecular distribution at the retinal-vitreous interface— into the VH chamber....
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TL;DR: The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied.
Abstract: In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [β2-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.
210 citations
Cites result from "Potential role and therapeutic inte..."
...In spite of these early data suggesting a role in uremic neurotoxicity, subsequent direct assessments of the impact of myoinositol on nervous function could not confirm this effect [25,82] and some studies even suggest a neuroprotective effect [83]....
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TL;DR: A nontargeted metabolomics approach using gas and liquid chromatography coupled to mass spectrometry to quantify 493 small molecules in human serum provides a comprehensive list of kidney function-associated metabolites and highlights potential novel filtration markers that may help to improve the estimation of GFR.
Abstract: Small molecules are extensively metabolized and cleared by the kidney. Changes in serum metabolite concentrations may result from impaired kidney function and can be used to estimate filtration (e.g., the established marker creatinine) or may precede and potentially contribute to CKD development. Here, we applied a nontargeted metabolomics approach using gas and liquid chromatography coupled to mass spectrometry to quantify 493 small molecules in human serum. The associations of these molecules with GFR estimated on the basis of creatinine (eGFRcr) and cystatin C levels were assessed in ≤1735 participants in the KORA F4 study, followed by replication in 1164 individuals in the TwinsUK registry. After correction for multiple testing, 54 replicated metabolites significantly associated with eGFRcr, and six of these showed pairwise correlation (r≥0.50) with established kidney function measures: C-mannosyltryptophan, pseudouridine, N-acetylalanine, erythronate, myo-inositol, and N-acetylcarnosine. Higher C-mannosyltryptophan, pseudouridine, and O-sulfo-L-tyrosine concentrations associated with incident CKD (eGFRcr <60 ml/min per 1.73 m2) in the KORA F4 study. In contrast with serum creatinine, C-mannosyltryptophan and pseudouridine concentrations showed little dependence on sex. Furthermore, correlation with measured GFR in 200 participants in the AASK study was 0.78 for both C-mannosyltryptophan and pseudouridine concentration, and highly significant associations of both metabolites with incident ESRD disappeared upon adjustment for measured GFR. Thus, these molecules may be alternative or complementary markers of kidney function. In conclusion, our study provides a comprehensive list of kidney function–associated metabolites and highlights potential novel filtration markers that may help to improve the estimation of GFR.
153 citations
TL;DR: It is timely to consider exploration of the roles and applications of the "other" isomers and their derivatives, likely by exploiting techniques now well developed for the myo series.
Abstract: Cell signaling via inositol phosphates, in particular via the second messenger myo-inositol 1,4,5-trisphosphate, and phosphoinositides comprises a huge field of biology. Of the nine 1,2,3,4,5,6-cyclohexanehexol isomers, myo-inositol is pre-eminent, with "other" inositols (cis-, epi-, allo-, muco-, neo-, L-chiro-, D-chiro-, and scyllo-) and derivatives rarer or thought not to exist in nature. However, neo- and d-chiro-inositol hexakisphosphates were recently revealed in both terrestrial and aquatic ecosystems, thus highlighting the paucity of knowledge of the origins and potential biological functions of such stereoisomers, a prevalent group of environmental organic phosphates, and their parent inositols. Some "other" inositols are medically relevant, for example, scyllo-inositol (neurodegenerative diseases) and d-chiro-inositol (diabetes). It is timely to consider exploration of the roles and applications of the "other" isomers and their derivatives, likely by exploiting techniques now well developed for the myo series.
133 citations
TL;DR: In this paper, the influence of feed restriction, anti-nutritional factors, structural components and feed additives on liver structure and function is discussed, and effects of feed technology techniques such as thermal treatment and pelleting, feed particle size and whole grain feeding on the liver are also reviewed.
Abstract: Despite having huge responsibilities in avian species, published reports on the influence of dietary factors and other possible constraints on the size, development and function of liver are limited. Consideration of the factors that could influence and alter liver function is therefore of critical relevance. In the current review, aspects of liver structure and function, and the influence of feed restriction, anti-nutritional factors, structural components and feed additives on liver are discussed. Effects of feed technology techniques such as thermal treatment and pelleting, feed particle size and whole grain feeding on the liver are also reviewed. A discussion of lipogenesis and lipid storage in poultry is presented to provide a better understanding and to differentiate the normal pathways of lipid metabolism from abnormal (i.e., disordered) pathways. The liver is the main site of fat synthesis in poultry, but under certain conditions, excessive fat can accumulate in the liver and cause problems. Factors contributing to the fatty liver syndrome are also examined.
122 citations
Cites result from "Potential role and therapeutic inte..."
...The results of several studies suggest that inositol plays an important role as a transporter of dietary fats [82,84]....
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References
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TL;DR: The article summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables and the need for standardisation of phYtic acid analysis in foods argued.
Abstract: The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.
675 citations
TL;DR: The information compiled under various subtitles of this article is derived from an enormous amount of data summarized in several excellent literature reviews, and thus their further reading is suggested to gain in-depth knowledge of each of the subject matter.
Abstract: Diabetic nephropathy is characterized by excessive amassing of extracellular matrix (ECM) with thickening of glomerular and tubular basement membranes and increased amount of mesangial matrix, which ultimately progress to glomerulosclerosis and tubulo-interstitial fibrosis. In view of this outcome, it would mean that all the kidney cellular elements, i.e., glomerular endothelia, mesangial cells, podocytes, and tubular epithelia, are targets of hyperglycemic injury. Conceivably, high glucose activates various pathways via similar mechanisms in different cell types of the kidney except for minor exceptions that are related to the selective expression of a given molecule in a particular renal compartment. To begin with, there is an obligatory excessive channeling of glucose intermediaries into various metabolic pathways with generation of advanced glycation products (AGEs), activation of protein kinase C (PKC), increased expression of transforming growth factor-β (TGF-β), GTP-binding proteins, and generation...
568 citations
"Potential role and therapeutic inte..." refers background in this paper
...Therefore, the depletion of MI plays an important role in the development and progression of diabetic nephropathy [46,52]....
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