The Free Myo‐inositol Concentration of Adult and Fetal Tissues of Several Species

Battaglia, Frederick C.; Meschia, Giacomo; Blechner, Jack N.; Barron, Donald H.

doi:10.1113/expphysiol.1961.sp001532

Cited by 37 publications

(32 citation statements)

References 2 publications

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“…The concentration of mI in neural cells is about 2 to 500 times that of plasma-a gradient for which a high affinity sodium-mI transporter (SMIT) is responsible. SMIT mRNA and protein expression are highest in the fetal brain, a fact reflected in the high concentration of mI in fetal CSF (21) and in the newborn brain (8). In fact, mI is the largest peak seen in proton spectra from normal newborn brain (22).…”

Section: Discussionmentioning

confidence: 99%

Proton Spectroscopy Detected Myoinositol in Children with Traumatic Brain Injury

et al. 2004

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Previous studies have shown that proton magnetic resonance spectroscopy (MRS) is useful in predicting neurologic prognosis in children with traumatic brain injury (TBI). Reductions in N-acetyl derived metabolites and presence of lactate have been predictive of poor outcomes. We examined another spectroscopy metabolite, myoinositol (mI), to determine whether it is altered after TBI. Found primarily in astrocytes, mI functions as an osmolyte and is involved in hormone response pathways and protein-kinase C activation. Myoinositol is elevated in the newborn brain and is increased in a variety of diseases. We studied 38 children (mean age 11 y; range 1.6 -17 y) with TBI using quantitative short echo time occipital gray and parietal white matter proton MRS at a mean of 7 d (range 1-17 d) after injury. We found that occipital gray matter mI levels were increased in children with TBI (4.30 Ϯ 0.73) compared with controls (3.53 Ϯ 0.48; p ϭ 0.003). We also found that patients with poor outcomes 6 -12 mo after injury had higher mI levels (4.78 Ϯ 0.68) than patients with good outcomes (4.15 Ϯ 0.69; p Ͻ 0.05). Myoinositol is elevated after pediatric TBI and is associated with a poor neurologic outcome. The reasons for its elevation remain unclear but may be due to astrogliosis or to a disturbance in osmotic function. Over the past decade, proton magnetic resonance spectroscopy (MRS) has been proven helpful in evaluating adults and children with traumatic brain injury (TBI) (1,2). Reductions in the neuronal marker N-acetyl aspartate (NAA) and in creatine (Cre), a marker of cell energy metabolism, as well as increases in choline (Cho), an indicator of membrane disruption, occur within the first several days. In adults, the magnitude of these metabolite changes correlate with the severity of injury and also with neurologic and neuropsychological outcomes (3,4). Our previous studies in children have also confirmed these findings (5,6).Myoinositol (mI) is another metabolite that can be detected using short echo time spectroscopy. Myoinositol is found primarily in astrocytes and functions as a marker of astrocytic activity. It serves as an osmolyte, and is involved in phosphoinositide-mediated signal transduction. Myoinositol as detected by MRS has been shown to be elevated in the newborn brain and is increased in Alzheimer's disease, renal failure, diabetes mellitus, bipolar disease, use of lithium, hypoxia, hyperosmolar states, in some patients with Canavan disease and after severe neonatal encephalopathy (7,8). It may be decreased in chronic hepatic encephalopathies, stroke, tumor, infection and low-grade malignancies.Within the first hours after TBI, the complex process referred to as reactive astrocytosis, astrogliosis, or glial scarring begins (9). After the initial injury, which is accompanied by ABSTRACT630

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Section: Discussionmentioning

confidence: 99%

Proton Spectroscopy Detected Myoinositol in Children with Traumatic Brain Injury

et al. 2004

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“…The concentrations of inositol in these tissues are very high at the earliest stages of development (12,13). The enzyme required for the synthesis of inositol from glucose (glucose-6-P cyclase) has been found in the human placenta and umbilical cord (9,14). However, nothing is known about whether fetal inositol requirements are met by placental transport or by fetal production.…”

Section: Discussionmentioning

confidence: 99%

Fetal and Maternal Non-glucose Carbohydrates and Polyols Concentrations in Normal Human Pregnancies at Term

Brusati

Jóźwik

et al. 2005

Pediatr Res

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The objective of the present investigation was to determine fetal and maternal plasma concentrations of nonglucose carbohydrates and polyols in normal human pregnancies at term. Uncomplicated human pregnancies (n ϭ 50) were studied at Ն37 wk gestation. Blood samples were obtained from umbilical artery, umbilical vein, and maternal peripheral blood at the time of elective cesarean section. Plasma concentrations of inositol, glycerol, erythritol, sorbitol, and mannose were determined by HPLC analysis. Differences between umbilical venous, umbilical arterial, and maternal concentration were tested by the two-tailed t test for paired samples. Correlations between umbilical and maternal concentration and between umbilical venoarterial concentration difference and umbilical arterial concentration were assessed by Pearson's correlation and multiple regression analysis. All newborns were appropriate for gestational age, and oxygenation and acid-base balance were within the normal range for all fetuses studied. For most of the polyols (inositol, sorbitol, and erythritol), the fetal concentration was significantly higher than the maternal concentration. The umbilical venoarterial concentration difference for inositol was Ϫ10.5 Ϯ 3.6 M, for glycerol was 10 Ϯ 1.7 M, for sorbitol was 3.8 Ϯ 0.5 M (p Ͻ 0.001), and for mannose was 7.6 Ϯ 0.7 M. There was a significant correlation between maternal concentration and umbilical venous concentration of mannose (UV MAN ϭ 15.38 ϩ 0.69 M MAN ; R 2 ϭ 0.46; p Ͻ 0.001). These results indicate that in normal human pregnancies at term, inositol is produced by the fetus, sorbitol is produced by the placenta, and there is a significant umbilical uptake of mannose from the maternal circulation. The transport of glucose across the human placenta has been well studied in both normal and high-risk pregnancies (1-4). However, the study of the other carbohydrates and sugar alcohols in plasma has received far less attention. In part, this may reflect the untested assumption that other carbohydrates and polyols can be produced from glucose in sufficient amounts to meet fetal requirements. One might assume, then, that there is little need for a supply of these other compounds to the fetus by placental transport. However, studies of the nutritional supply of amino acids in early development have emphasized that many amino acids that are considered "nonessential" may be required in the dietary supply to the fetus or the newborn (5,6). The same may be true of some carbohydrates. Recent studies have suggested that mammalian cells may require an exogenous supply of mannose to meet mannose 6-phosphate requirements for glycoprotein synthesis (7). Furthermore, the biologic importance of the polyols has received attention with respect to their accumulation in reproductive tissues (8 -10) and to their roles in complications of diabetes (11,12). A recent study demonstrated that a low maternal serum inositol concentration is associated with a 2.6-fold increased risk for offspring with spina bifida (13). In additio...

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“…SMIT1 has a slow substrate turnover rate of only a few per second, transporting 1 myo-inositol together with 2 Na + (21). The myo-inositol level in mammalian tissues ranges from 0.1 to 16 mM, depending on the tissue (22,23). It is high in adult brain (millimolar level) and is reduced by 96% in SLC5A3 −/− mice (24).…”

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confidence: 99%

Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P₂levels

Dai

Hou

Kruse

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Myo-inositol is an important cellular osmolyte in autoregulation of cell volume and fluid balance, particularly for mammalian brain and kidney cells. We find it also regulates excitability. Myo-inositol is the precursor of phosphoinositides, key signaling lipids including phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ]. However, whether myo-inositol accumulation during osmoregulation affects signaling and excitability has not been fully explored. We found that overexpression of the Na + /myo-inositol cotransporter (SMIT1) and myoinositol supplementation enlarged intracellular PI(4,5)P 2 pools, modulated several PI(4,5)P 2 -dependent ion channels including KCNQ2/3 channels, and attenuated the action potential firing of superior cervical ganglion neurons. Further experiments using the rapamycinrecruitable phosphatase Sac1 to hydrolyze PI(4)P and the P4M probe to visualize PI(4)P suggested that PI(4)P levels increased after myoinositol supplementation with SMIT1 expression. Elevated relative levels of PIP and PIP 2 were directly confirmed using mass spectrometry. Inositol trisphosphate production and release of calcium from intracellular stores also were augmented after myo-inositol supplementation. Finally, we found that treatment with a hypertonic solution mimicked the effect we observed with SMIT1 overexpression, whereas silencing tonicity-responsive enhancer binding protein prevented these effects. These results show that ion channel function and cellular excitability are under regulation by several "physiological" manipulations that alter the PI(4,5)P 2 setpoint. We demonstrate a previously unrecognized linkage between extracellular osmotic changes and the electrical properties of excitable cells.myo-inositol | ion channels | PIP 2 | phosphoinositide | SMIT1

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The Free Myo‐inositol Concentration of Adult and Fetal Tissues of Several Species

Cited by 37 publications

References 2 publications

Proton Spectroscopy Detected Myoinositol in Children with Traumatic Brain Injury

Proton Spectroscopy Detected Myoinositol in Children with Traumatic Brain Injury

Fetal and Maternal Non-glucose Carbohydrates and Polyols Concentrations in Normal Human Pregnancies at Term

Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P₂levels

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The Free Myo‐inositol Concentration of Adult and Fetal Tissues of Several Species

Cited by 37 publications

References 2 publications

Proton Spectroscopy Detected Myoinositol in Children with Traumatic Brain Injury

Proton Spectroscopy Detected Myoinositol in Children with Traumatic Brain Injury

Fetal and Maternal Non-glucose Carbohydrates and Polyols Concentrations in Normal Human Pregnancies at Term

Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2levels

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Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P₂levels