Serum Myo-inositol Research Articles

Enzymatic assay of myo-inositol in serum.

An enzymatic spectrophotometric method for determination of myo-inositol in serum is described. The method is sensitive and rapid to perform without special equipment. Linearity between the amount of myo-inositol and absorbance was obtained in the range of 0.5 to 3 nmol myo-inositol per assay. The amounts of myo-inositol determined in sera from apparently healthy subjects agree well with gas chromatographic data.

Myoinositol in Small Preterm Infants

Summary: Serum myoinositol (henceforth called inositol) concentration was measured in 12 preterm infants (birth weight 800–1,700 g, gestational age 27–32 weeks) from birth to 10 postnatal weeks. The diet was analyzed for inositol concentration and the daily intake was correlated with serum inositol. There were striking differences in the inositol concentration of infant feedings: preterm colostrum 4.22 ± 0.51 mM; term colostrum 2.91 ± 0.21 mM; mature milk 1.81 ± 0.20 m M; infant formulas 0.09–0.39 m M; parenteral nutrition 0.15 ± 0.13 m M. The high fetal serum inositol often fell during the first 2 weeks. After 2 weeks, serum inositol correlated significantly with inositol intake (R = 0.601, p < 0.004). On breast milk serum inositol concentrations (0.56 ± 0.07 m M) were higher than on formula feedings (0.36 ± 0.03 m M). Since according to animal studies inositol is important during prenatal growth and differentation, the present data justify further study on importance of dietary inositol in preterm infants.

Myoinositol in small preterm infants: relationship between intake and serum concentration.

Serum myoinositol (henceforth called inositol) concentration was measured in 12 preterm infants (birth weight 800-1,700 g, gestational age 27-32 weeks) from birth to 10 postnatal weeks. The diet was analyzed for inositol concentration and the daily intake was correlated with serum inositol. There were striking differences in the inositol concentration of infant feedings: preterm colostrum 4.22 +/- 0.51 mM; term colostrum 2.91 +/- 0.21 mM; mature milk 1.81 +/- 0.20 mM; infant formulas 0.09-0.39 mM; parenteral nutrition 0.15 +/- 0.13 mM. The high fetal serum inositol often fell during the first 2 weeks. After 2 weeks, serum inositol correlated significantly with inositol intake (R = 0.601, p less than 0.004). On breast milk serum inositol concentrations (0.56 +/- 0.07 mM) were higher than on formula feedings (0.36 +/- 0.03 mM). Since according to animal studies inositol is important during prenatal growth and differentiation, the present data justify further study on importance of dietary inositol in preterm infants.

Perinatal development of myoinositol uptake into lung cells: surfactant phosphatidylglycerol and phosphatidylinositol synthesis in the rabbit.

It has been proposed that the high serum myoinositol promotes fetal growth and affects development of lung surfactant. However, it is unclear how the extracellular myoinositol becomes available in specific cells and whether there are developmental differences in myoinositol uptake. In the present study the mechanisms and perinatal development of intracellular myoinositol uptake into rabbit lung cells were investigated. Lung slices, lung explants, and type II alveolar cells were used. Evidence of saturable, sodium- and energy-dependent, and of non-saturable, sodium- and energy-independent myoinositol uptake was found. The nonsaturable uptake decreased by 67% during spontaneous maturation, as studied in lung slices. Beta-methasone (0.2 mg/kg days 26.3 and 27.3, to the doe) decreased by 65% the nonsaturable myoinositol uptake in 28-day-old fetuses. However, the saturable uptake revealed only small changes during perinatal development. The effect of extracellular myoinositol on surfactant phospholipid synthesis was evaluated in lung explants from 28-day-old fetuses, cultured for 2 days. In the presence of 10(-6) M dexamethasone the concentration of extracellular myoinositol, required for half-maximal inhibition of surfactant phosphatidylglycerol incorporation was higher than in explants grown without the hormone (approximately 0.4 versus 0.2 mM). However, in the microsomal fraction the phosphatidylglycerol incorporation was always inhibited by as low as 4 microM myoinositol. Myoinositol was taken up by isolated type II cells preferably by nonsaturable mechanism. The phosphatidylglycerol incorporation was less sensitive to extracellular myoinositol in adult than in fetal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzymatic assay of myo-inositol in serum

Enzymatic assay of myo-inositol in serum

Relationship between serum myo-inositol and peripheral neuropathy in patients with chronic renal failure

Relationship between serum myo-inositol and peripheral neuropathy in patients with chronic renal failure

Role of myoinositol in regulation of surfactant phospholipids in the newborn.

According to animal studies myoinositol decreases surfactant phosphatidylglycerol and increases phosphatidylinositol. In the present study lung effluent phospholipids and serum myoinositol were analyzed in respiratory distress syndrome (RDS, 19 cases), in other lung disease (6 cases) and in 22 newborn with no lung disease. In addition, myoinositol was studied in amniotic fluid and in serum from umbilical vessels and from maternal vein (15 healthy newborn). There was a significant correlation between the fetal and amniotic fluid levels of myoinositol, but no detectable correlation between fetal and maternal myoinositol. Serum myoinositol was higher in preterm than in term newborns. In healthy newborns there was a negative correlation between lung effluent phosphatidylglycerol (expressed as percent of the phospholipids) and serum myoinositol (r = -0.968), and a positive linear correlation between myoinositol and lung effluent phosphatidylinositol (r = 0.849). In RDS at birth, undetectable phosphatidylglycerol corresponded with high serum myoinositol. During the first 5 neonatal days serum myoinositol either (1) decreased and phosphatidylglycerol appeared, (2) remained high and phosphatidylglycerol correspondingly low in some small preterm infants, or (3) decreased but phosphatidylglycerol did not expectedly increase and disaturated lecithin/sphingomyelin ratio remained low in other small preterm babies. We propose that a premature decrease in serum myoinositol among small preterm infants with RDS is not beneficial, since myoinositol may promote hormone-induced lung maturation and healing of lung damage.

SURFACTANT SUBSTITUTION IN RDS. AN EVALUATION OF THE TURNOVER OF EXOGENEOUS AND ENDOGENEOUS SURFACTANT

A potential side effect of exogeneous surfactant is inhibition of the endogeneous surfactant secretion. We have studied this question. Human surfactant (HS, 120 mg/kg) was given before the age of 10 h, in order to treat severe RDS. Tracheal aspirates (N=128) were recovered from ten infants (BW 1013±285 g; GA '27.4±1.1 w; 5 received HS, 5 controls) and analyzed for phospholipids. The interpretation of the results is based upon the following knowledge: 1. In tracheal aspirate the phospholipid composition is similar to that in alveolar lavage. 2. Surfactant phospholipids from RDS and from no-RDS are similar except for the acidic phospholipids: in RDS there is only phosphatidylinositol (PI), whereas normal surfactant contains both PI and phosphatidylglycerol (PG). 3. The high serum myoinositol in RDS prevents PG synthesis (J.Clin.Invest. 68, 742,1981). The turnover of exogeneous HS was measured on the basis of the exponential decay data of PG/(PG+PI)-ratio. The half-life of PG was 33±5 h. HS substitution increased HS pool size 5-22-fold, and increased saturated lecithin/sphingomyelin (L/S) from 3.0±0.4 to 25.0±8.3. Subsequently L/S remained high and the respiratory status improved. At the age of one week the treated infants had higher L/S than the controls (22.4±3.7 vs 9.4±1.7). According to present evidence exogeneous HS did not suppress endogeneous HS secretion. Instead, exogeneous HS may be utilized for endogeneous synthesis of surfactant.

Effect of extracellular myo-inositol on surfactant phospholipid synthesis in the fetal rabbit lung

In the present investigation, myo-inositol was elevated in fetal serum by dietary manipulation. The myo-inositol-containing diet doubled the already high fetal serum myo-inositol between fetal days 26 and 28 but had no detectable effects on the lung. However, myo-inositol decreased betamethasone-induced (0.2 mg/kg, days 26.3 and 27.3, to the doe) inhibition in lung growth and potentiated the hormone-induced increase in alveolar space saturated phosphatidylcholine. This effect could not be explained by alteration of glucocorticoid-stimulated enzyme activity (phosphatidate cytidylyltransferase, phosphatidic acid phosphohydrolase, choline phosphate cytidylyltransferase) in the lung. Lung explants from 26-day-old fetuses were grown in a serum-free medium for 4 days. myo-Inositol (1.5 mM) had only a small effect on the phospholipid incorporation. Dexamethasone and thyroxine increased the incorporation of the precursors into surfactant phosphatidylglycerol and saturated phosphatidylcholine. myo-Inositol, in the presence of the hormones, switched the acidic surfactant phospholipid from phosphatidylglycerol to phosphatidylinositol and further increased the incorporation of surfactant-associated saturated phosphatidylcholine. myo-Inositol-excess preferentially increased the incorporation of NADPH (derived from glucose) and acetate into the fatty acid moiety of surfactant phosphatidylcholine. It is proposed that the high extracellular myo-inositol in immature fetuses provides an environment that promotes both the hormone-stimulated differentiation and the growth.

Effect of myo-inositol on the glycerophospholipid composition of adult and fetal rat lung tissue.

In many species including man, the second most abundant lipid in lung surfactant is phosphatidylglycerol (PG) which may comprise 10% of the total lipid in surfactant from mature lungs. Infants delivered before their surfactant contained a large amount of PG are at greater risk of succumbing to hyaline membrane disease. Regulation of the PG content of lung surfactant is not understood completely, but the reciprocal changes in the amount of phosphatidylinositol (PI) and PG in surfactant as the lung mature are suggestive of regulation at the level of a common precursor. The immediate common precursor of PI and PG is CDP-diacylglycerol which is found in only small amounts in most mammalian cells and likely restricts the biosynthesis of both PI and PG. It has been observed in several species that the enzymes that synthesize PI and PG compete for the limited amount of CPD-diacylglycerol and this competition is influenced by the availability of myo-inositol. We and others have presented evidence that myo-inositol availability in the developing lung may be an important factor in the regulation of lung surfactant composition. In the present investigation, myo-inositol was administered chronically to nonpregnant and to pregnant rats and the effect of this treatment on the glycerophospholipid composition of lung tissue and lung lavage was measured. In addition, the influence of myo-inositol administration to pregnant rats on the glycerophospholipid composition of lung tissue of their fetuses was investigated. The concentration of myo-inositol in adult and fetal blood was measured by gas-liquid chromatography of its trimethylsilyl derivative. For determination of glycerophospholipid composition, the total lipid extracts of lung tissues and lung lavage were separated by 2-dimensional thin-layer chromatography and quantified by lipid phosphorus assay of individual spots. The concentration of myo-inositol in the serum of pregnant rats was significantly higher than in nonpregnant rats (Tab. I, Fig. 1). Treatment of the rats with myo-inositol resulted in a significant elevation of serum concentrations of myo-inositol throughout the experimental period. Between day 18 and day 21 of the gestation there was a significant decrease in serum myo-inositol concentrations in fetuses of saline treated rats. Treatment of the pregnant dams with myo-inositol resulted in a significant elevation in fetal serum concentrations of myo-inositol on both day 18 and day 21 of gestation (Tab. I).(ABSTRACT TRUNCATED AT 400 WORDS)

Pathogenetic aspects of respiratory distress syndrome in adults and newborns. Experimental and clinical data.

Activation of the kallikrein-kinin system was demonstrated in experimental lung failure in dogs and respiratory distress syndrome (RDS) in newborns. Further lung damage was found in rats after intravenous infusion of hypoxanthine during exposure to 100% oxygen for 48 h. It is discussed whether such damage was mediated through free oxygen radicals produced by the hypoxanthine-xanthine oxidase system. Newborn babies with RDS had high serum myoinositol levels and the role of myoinositol as regulator of surfactant synthesis is discussed. These three different approaches demonstrate the complexity of pathogenesis of RDS in newborn babies and adults.

The influence of myo-inositol on phosphatidylglycerol synthesis by rat type II pneumonocytes.

Type II pneumonocytes isolated from adult rat lung were incubated in a serum-free medium containing [14C]glycerol and the incorporation of 14C into glycerophospholipids was measured. After 24 h, more than 80% of the 14C incorporated into total lipids or into phosphatidylcholine and approx. 90% of the 14C incorporated into phosphatidylglycerol after 24 h was recovered in the glycerophosphoester moieties of these molecules. Supplementation of the incubation medium with foetal-bovine serum (10%, v/v) did not alter the incorporation of [14C]glycerol by type II pneumonocytes after 24 h into either a total lipid extract or phosphatidylcholine. In the presence of foetal-bovine serum, however, the incorporation of 14C into phosphatidylglycerol was decreased and the incorporation of 14C into phosphatidylinositol was increased. In the absence of foetal-bovine serum, the incorporation of 14C into phosphatidylglycerol was decreased progressively as the concentration of myo-inositol in the incubation medium was increased. The range of concentration (0.04-0.50 mM) over which myo-inositol had the greatest influence on [14C]glycerol incorporation into phosphatidylglycerol by type II pneumonocytes in vitro encompassed the concentration range measured in foetal-rat serum late in gestation. At 4 days before birth, the concentration of myo-inositol in foetal-rat serum was 0.36 mM and decreased to 0.23 mM 1 day before birth. The concentration of myo-inositol in adult rat serum increased from 0.03 mM to 0.06 mM during pregnancy. Isolated rat type II pneumonocytes were found to take up myo-inositol by a saturable process. A half-maximal rate of myo-inositol uptake occurred at a concentration of myo-inositol of 0.29 mM. The results of this investigation are consistent with the hypothesis that late in gestation there is a decreasing availability of myo-inositol to the foetal lungs and that this favours the biosynthesis of phosphatidylglycerol for surfactant at the expense of phosphatidylinositol biosynthesis.

Myo-inositol homeostasis in foetal rabbit lung.

In several species, lung maturation is accompanied by a decline in the phosphatidylinositol content of lung surfactant and a concomitant increase in its phosphatidylglycerol content. To examine the possibility that this developmental change is influenced by the availability of myo-inositol, potential sources of myo-inositol for the developing rabbit lung were investigated. On day 28 of gestation the myo-inositol content of foetal rabbit lung tissue (2.3+/-0.5mumol/g of tissue) was not significantly different from that of adult lung tissue but the activity of d-glucose 6-phosphate:1l-myo-inositol 1-phosphate cyclase (cyclase) in foetal lung tissue (81.0+/-9.0nmol.h(-1).g of tissue(-1)) was higher than that found in adult lung tissue (23.2+/-1.0nmol.h(-1).g of tissue(-1)). Day 28 foetal rabbit lung tissue was found also to take up myo-inositol by a specific, energy-dependent, Na(+)-requiring mechanism. Half-maximal uptake of myo-inositol by foetal rabbit lung slices was observed when the concentration of myo-inositol in the incubation medium was 85mum. When the myo-inositol concentration was 1mm (but not 100mum) the addition of glucose (5.5mm) stimulated myo-inositol uptake. myo-Inositol uptake was observed also in adult rabbit lung and was found to be sub-maximal at the concentration of myo-inositol found in adult rabbit serum. The concentration of myo-inositol in the serum of pregnant adult rabbits (47.5+/-5.5mum) was significantly lower than that of non-pregnant adult female rabbits (77.9+/-9.2mum). On day 28 of gestation the concentration of myo-inositol in foetal serum (175.1+/-12.0mum) was much less than on day 25, but more than that found on day 30. A transient post-partum increase in the concentration of myo-inositol in serum was followed by a rapid decline. Much of the myo-inositol in foetal rabbit serum probably originates from the placenta, where on day 28 of gestation a high cyclase activity (527+/-64nmol.h(-1).g of tissue(-1)) was measured. The gestational decline in serum myo-inositol concentration, together with the decreasing cyclase activity of the lungs, is consistent with the view that maturation of the lungs is accompanied by decreased availability of myo-inositol to this tissue.

1461 INDUCED FETAL HYPERINSULINEMIA AND MACROSOMIA

Human gestational diabetic pregnancies are associated with fetal macrosomia & delayed surfactant production, especially phosphatidylglycerol (PG). Excess serum myoinositol is associated with delayed appearance of PG.Three female rabbits, with dated 27 day pregnancies were infused with D15/.2% saline for 48 hours (15 mg glucose/kg/min). Three controls were infused with D4/.2% saline for 48 hours (3 mg glucose/kg/min). Seventy-three fetuses were delivered at 29 days gestation. Although not all D15 treated fetuses were hyperinsulinemic, fetuses were easily divided into low insulin (<82 μU/ml) and high insulin (>140 μU/ml) groups.Alveolar lavages of fetal lungs with saline were examined for phospholipids, but no differences were found in percentages of sphingomyelin, phosphatidylcholine, phosphatidylinositol, phosphatidylserine, or phosphatidylethanolamine. PG was undetectable in all specimens.Previous animal models for diabetic pregnancy have produced severe diabetes with anti-beta cell compounds administered to the mother. Fetal wastage & growth retardation often result. This model produces a late gestational hyperglycemic state with fetal hyperinsulinemia, macrosomia, & increased serum myoinositol.