Dietary Myo-inositol Supplementation Research Articles

Myo-inositol improves osmoregulation by promoting lipid utilization in Nile tilapia (Oreochromis niloticus)

This research explores the influence of myo-inositol (MI) on the hypertonic stress adaptation of Nile tilapia (Oreochromis niloticus) by increasing lipid utilization under long-term salinity stress. A two-factor interactive experiment was used, and diets containing either normal lipids (NL, 7%) or high lipids (HL, 15%) contained three MI concentrations of 0, 400, and 1200 mg/kg in each lipid diet. Fish were fed six diets under 20 psu (practical salinity units [psu]) for eight weeks. Under long-term hypertonic stress, dietary MI supplementation significantly improved the growth performance of O. niloticus (P < 0.05). Dietary 1200 mg/kg MI supplementation significantly promoted protein deposition and reduced fat accumulation in the whole fish (P < 0.05). The HL diet significantly caused lipid accumulation in the liver, while dietary 1200 mg/kg MI addition alleviated lipid accumulation by promoting the expression of genes related to lipolysis (PPAR-α; ATGL and CPT) and inhibiting the expression of genes related to lipid synthesis (SREBP; DGAT and FAS) (P < 0.05). In addition, 400 mg/kg MI significantly reduced serum lipids (TG and LDL-C) (P < 0.05). qPCR showed that the purity of dietary 1200 mg/kg MI significantly upregulated the expression of an ion transporter-related gene (NKA) in gills (P < 0.05). Meanwhile, 400 mg/kg and 1200 mg/kg MI significantly affected the content of fatty acids in the liver and gill (P < 0.05). In addition, dietary 1200 mg/kg MI supplementation significantly increased the antioxidant capacity in the liver of O. niloticus. In conclusion, dietary supplementation with 1200 mg/kg MI could regulate lipid metabolism, promote lipid utilization and improve the osmotic regulation ability of O. niloticus.

Regulatory role of myo-inositol in the ovarian development of female Chinese mitten crab (Eriocheir sinensis)

The ovarian development of female crab can directly affect the nutritional value, broodstock fertility and health status of offspring and are essential for the success of the crab industry. This study evaluates the influences of dietary myo-inositol (MI) on the ovarian development of female Chinese mitten crab (Eriocheir sinensis). Three diets containing different MI levels (0, 1600 and 3200 mg/kg) were fed to 144 crabs (initial weight: 72.38 ± 2.53 g) for 13 weeks. Crabs fed the diets with 1600, and 3200 mg/kg MI supplementation had significantly higher gonadosomatic index and yolk granule deposition in the ovary than those fed diets without MI supplementation. Crabs fed 1600 and 3200 mg/kg MI supplementation significantly enhanced vitellogenin synthesis in the hepatopancreas, vitellogenin contents in the hemolymph and vitellogenin receptor mRNA level in the ovary compared with those fed diets without MI supplementation. Simultaneously, cyclic adenosine monophosphate content and gene expression of retinoid X receptor, protein kinase A and ecdysteroid receptor in the hepatopancreas, and ecdysteroid content in hemolymph significantly increased when 1600 and 3200 mg/kg MI were supplemented in diets. Moreover, crabs fed 1600 and 3200 mg/kg MI supplementation had significantly higher lipid content in the ovary than those fed the diets without MI supplementation. The neutral lipid content in the hepatopancreas tended to decrease as the dietary MI level increased, while the polar lipid content in the hepatopancreas and the neutral and polar lipid contents in the ovary tended to increase. Dietary MI supplementation significantly enhanced the expression of genes related to lipid catabolism, lipid absorption and transport in the hepatopancreas, and gene expression related to lipid absorption in the ovary, suggesting that MI could promote the transport of lipids to the ovary from the hepatopancreas for ovarian development. This study indicates that dietary 1600 mg/kg MI supplementation is sufficient to promote the ovarian development of E. sinensis.

Enhancement of protein deposition and meat quality of male Chinese mitten crab (Eriocheir sinensis): Application of myo-inositol in crustacean nutrition

The nutritional value and meat quality influence the consumer preference for crab. Dietary nutrition manipulation is a practical way to regulate flesh quality. This study evaluates the effects of dietary myo-inositol on the nutritional value and meat flavor of male Chinese mitten crab (Eriocheir sinensis). Three diets supplemented with different myo-inositol levels (0, 1600 and 3200 mg/kg) were fed to the crabs for 12 weeks. Dietary myo-inositol supplementation significantly increased the content of highly unsaturated fatty acids in the muscle and enhanced muscle protein deposition by up-regulating the expression of genes related to protein synthesis in the crab muscle. Metabolome analysis showed that the differential metabolites were enriched in the amino acid metabolic process in the groups with myo-inositol supplementation. Moreover, the content of total umami-free amino acids increased when crabs were fed diets with myo-inositol supplementation, which may relate to the production of umami flavor in crabs. Therefore, myo-inositol supplementation may be a practical approach to improving the meat quality of male E. sinensis.

New insights into the influence of myo-inositol on carbohydrate metabolism during osmoregulation in Nile tilapia (Oreochromis niloticus).

A two-factor (2 × 3) orthogonal test was conducted to investigate the effects of dietary myo-inositol (MI) on the osmoregulation and carbohydrate metabolism of euryhaline fish tilapia (Oreochromis niloticus) under sustained hypertonic stress (20 practical salinity units [psu]). 6 diets containing either normal carbohydrate (NC, 30%) or high carbohydrate (HC, 45%) levels, with 3 levels (0, 400 and 1,200 mg/kg diet) of MI, respectively, were fed to 540 fish under 20 psu for 8 weeks. Dietary MI supplementation significantly improved growth performance and crude protein content of whole fish, and decreased the content of crude lipid of whole fish (P < 0.05). Curled, disordered gill lamella and cracked gill filament cartilage were observed in the gill of fish fed diets without MI supplementation. The ion transport capacity in gill was significantly improved in the 1,200 mg/kg MI supplementation groups compared with the 0 mg/kg MI groups (P < 0.05). Moreover, the contents of Na+, K+, Cl− in serum were markedly reduced with the dietary MI supplementation (P < 0.05). The fish fed 1,200 mg/kg MI supplementation had the highest MI content in the gills and the lowest MI content in the serum (P < 0.05). Additionally, the fish fed with 1,200 mg/kg MI supplementation had the highest MI synthesis capacity in gills and brain (P < 0.05). Dietary MI markedly promoted the ability of carbohydrate metabolism in liver (P < 0.05). Moreover, fish in the 1,200 mg/kg MI groups had the highest antioxidant capacity (P < 0.05). This study indicated that high dietary carbohydrate would intensify stress, and impair the ability of osmoregulation in tilapia under a long-term hypersaline exposure. The supplementation of MI at 1,200 mg/kg in the high carbohydrate diet could promote carbohydrate utilization and improve the osmoregulation capacity of tilapia under long-term hypertonic stress.

Effect of antenatal dietary myo-inositol supplementation on the incidence of gestational diabetes mellitus and fetal outcome: protocol for a double-blind randomised controlled trial

IntroductionGestational diabetes mellitus (GDM) affects 23.6% of Qatari women and is associated with maternal and perinatal morbidity and long-term risk of developing type 2 diabetes. A number of challenges exist...

Toxicity of chronic copper exposure on Chinese mitten crab (Eriocheir sinensis) and mitigation of its adverse impact by myo-inositol

Copper (Cu) is a widespread pollutant in water and has posed a significant threat to aquatic animals' health. It is essential to find a strategy to reduce the adverse effects of copper on aquatic organisms. This study investigated the role of myo-inositol (MI) in the reducing chronic toxicity induced by copper in Chinese mitten crab (Eriocheir sinensis). Two diets, including 0 mg/kg and 1600 mg/kg MI were fed to crabs exposed to 0 μg/L and 40 μg/L Cu2+ for 7 weeks. Dietary MI could improve the decreased weight gain and specific growth rate induced by copper exposure. Copper exposure increased the copper levels in the whole body and hepatopancreas, increased the malondialdehyde content, and suppressed the antioxidant enzymes system of the crabs. Simultaneously, copper exposure induced DNA fragmentation, decreased the gene expression/activities of immune-related genes/enzymes and the expression of the anti-apoptotic genes, and increased the gene expression of heat shock protein 70 and pro-apoptotic genes. The mitochondrial dysfunction, increased the gene expression of inflammation-related genes and caused the higher activity of damage-related enzymes in the crabs under Cu exposure. The administration of dietary MI markedly ameliorated the copper-induced oxidative stress, immune and hepatopancreas damage, mitochondrial dysfunction, apoptosis and inflammatory responses. This study indicates that dietary MI supplementation can effectively alleviate the negative effect of chronic copper exposure on E. sinensis.

Growth, osmotic response and transcriptome response of the euryhaline teleost, Oreochromis mossambicus fed different myo-inositol levels under long-term salinity stress

Myo-inositol (MI) as a major intracellular osmolyte can be accumulated to protect cells from a variety of stress. The present study was to evaluate the effects of dietary MI on growth, osmotic response and transcriptional response in the liver of euryhaline fish Oreochromis mossambicus under long-term salinity stress. Five isonitrogenous and isolipidic diets were formulated to include 0 (MI0), 200 (MI200), 400 (MI400), 800 (MI800) and 1600 (MI1600) mg/kg MI. In this study, dietary 400 mg/kg MI significantly increased the weight gain and specific growth rate of O. mossambicus compared with the group without dietary MI supplementation under salinity stress. Moreover, dietary MI decreased serum glucose and insulin levels of fish under long-term salinity stress. Fish fed 400 mg/kg MI supplementation had significantly higher serum cortisol, sodium (Na+) and chloride ion (Cl−) than those fed a diet without MI supplementation. A total of 132.17 million and 115.8 million clean reads were obtained from the 0 mg/kg MI (MI0) and 400 mg/kg (MI400) MI group respectively. Compared with the MI0 group, the expression of 704 genes was significantly changed (521-up and 183-down) in the MI400 group under long-term salinity stress. Transcriptome results indicate that myo-inositol can regulate lipid and pyruvic acid metabolism, increase phospholipid synthesis-related mRNA levels and improve antioxidant properties of O. mossambicus under long-term salinity stress. This study suggests that optimum MI supplementation is 400 mg/kg in the diet based on weight gain against dietary MI and this result provides a nutritional solution for tilapia to cope with salinity stress.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: study protocol for a randomized controlled trial

BackgroundGestational diabetes mellitus (GDM) is defined as impaired glucose tolerance with onset or first recognition during pregnancy, which is characterized by an increased insulin resistance. Gestational diabetes mellitus is associated with pregnancy-related maternal and fetal morbidity (both antenatal and perinatal).Myo-inositol has been suggested to improve insulin resistance in women with polycystic ovary syndrome.The aim of this study is to examine the impact of myo-inositol supplementation during pregnancy on the incidence of gestational diabetes mellitus.MethodsWe will conduct a single-center, open-label, randomized controlled trial. A total of 160 healthy pregnant women with singleton pregnancy at 11–13+6 weeks of gestation will be randomly allocated in two groups: intervention group (N = 80) and control group (N = 80). The intervention group will receive myo-inositol and folic acid (4000 mg myo-inositol and 400 mcg folic acid daily) from 11 to 13+6 weeks of gestation until 26–28 weeks of gestation, while the control group will receive folic acid alone (400 mcg folic acid daily) for the same period of time as intervention group. The primary outcome will be gestational diabetes incidence rate at 26–28 weeks of gestation, according to the results of a 75 g oral glucose tolerance test held at 26–28 weeks of gestation. The secondary outcomes will include fasting blood glucose levels, glycated hemoglobin levels, insulin resistance level (evaluated by homeostasis model assessment of insulin resistance and Matsuda Index), and incidence rate of diet-treated gestational diabetes and diabetes requiring insulin therapy at 26–28 weeks of gestation.DiscussionThis trial will provide evidence for the effectiveness of myo-inositol supplementation during pregnancy in reducing the incidence of gestational diabetes mellitus.Trial registrationISRCTN registry: ISRCTN16142533. Registered on 9 March 2017.

Changes in growth performance, aflatoxin B1 residues, immune response and antioxidant status of Litopenaeus vannamei fed with AFB1-contaminated diets and the regulating effect of dietary myo-inositol supplementation

This study aimed to investigate if myo-inositol (MI) supplementation could alleviate adverse effects caused by aflatoxin B1 (AFB1) with respect to growth performance, AFB1 residues, immune response and antioxidant status of Litopenaeus vannamei. 800 shrimp (initial weight: 1.1 g) were divided into five groups: MI0 (basal diet); MI0 + LA, MI0 + HA, MI200 + LA and MI200 + HA fed with AFB1-contaminated diets (LA, low concentration AFB1; HA, high concentration AFB1; MI200, adding 200 mg MI kg−1 diet). The results showed that HA significantly decreased growth performance, systemic inositol content and lipid content. AFB1 residues were detected in the hepatopancreas of shrimp, but not the muscle. Histological lesions were observed in MI0 + LA and MI0 + HA groups. HA supplementation raised malondialdehyde and protein carbonyl content and reduced some antioxidant enzyme activities and immune-related genes expression, which was slightly ameliorated by MI supplementation. Our results suggest that myo-inositol may slightly mitigate negative impacts caused by AFB1 in L. vannamei.

Dietary myo‐inositol requirements of juvenile hybrid sturgeon ( Acipenser baerii ♀ × A. schrenckii ♂ )

This study was conducted to determine the optimal dietary myo-inositol (MI) requirement of juvenile hybrid sturgeon (Acipenser baerii ♀ × A. schrenckii ♂). Fish with an initial average body weight of 28.28 ± 0.41 g were randomly divided into six groups with three repetitions in each group and fed the experimental diets with different graded MI concentrations (70.2, 130.0, 270.2, 443.0, 1,096.6 and 1997.3 mg/kg) three times per day for 12 weeks. The results showed that with the increase in dietary MI level from 70.2 mg/kg to 443.0 mg/kg, weight gain (WG) was increased significantly (p < .05); however, when the MI level was further increased, there was no significant difference in weight gain rate (WG) over time (p > .05). Specific growth rate (SGR) showed a similar trend. The feed conversion ratio (FCR), survival rate (SR), hepatosomatic index (HSI), viscerasomatic index (VSI) and condition factor (CF) were not affected by dietary MI supplementation (p > .05). Dietary MI did not affect whole-body and muscle crude protein and ash content (p > .05), while dietary MI significantly affected the muscle and whole-body crude lipid and moisture content (p < .05). Moreover, serum triglyceride (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were decreased by increasing dietary MI levels. Total antioxidant capacity (T-AOC), malonic dialdehyde (MDA) and superoxide dismutase (SOD) activities in the liver were also affected by the dietary MI (p < .05). In summary, this study indicated that the optimal dietary MI requirement for juvenile hybrid sturgeon (Acipenser baerii ♀ × A. schrenckii ♂) was 335.84 mg/kg and 590.65 mg/kg based on the maximum WG and liver MI accumulation indices respectively.

Changes in growth performance, haematological parameters, hepatopancreas histopathology and antioxidant status of pacific white shrimp (Litopenaeus vannamei) fed oxidized fish oil: Regulation by dietary myo-inositol

A 58-day feeding trial was conducted to evaluate the effects of dietary myo-inositol (MI) supplementation on growth performance, haematological parameters, hepatopancreas histopathology and antioxidant status of Litopenaeus vannamei fed with oxidized fish oil (OFO). Control diet contained fresh fish oil (FFO) without MI supplementation. The other four diets contained two oxidation levels of OFO (peroxide value: 133.2 and 268.7 meq kg−1) with or without 200 mg MI kg−1 diets (MI0+L, MI0+H, MI200 + L and MI200 + H). Results showed that OFO-supplemented groups (without MI supplementation) showed better growth performance and lower whole-body inositol content when opposed to control group. MI supplementation significantly improved whole-body inositol content in high-oxidized fish oil (HOFO) groups, and also reduced whole-body lipid in low-oxidized fish oil (LOFO) groups. Moreover, Supplementation of OFO and MI markedly hit the fatty acid profile of muscle. HOFO caused severe histopathological changes in hepatopancreas of shrimp, which slightly alleviated by MI supplementation. MI supplementation also grew the total protein (TP) content and alkaline phosphatase (AKP) activity and decreased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of serum in OFO-supplemented groups. Ingestion of OFO increased levels of lipid peroxidation and protein oxidation in serum or hepatopancreas, which partly ameliorated by MI supplementation. Activities of antioxidant enzymes exhibited different expression patterns because of OFO and MI. In addition, HOFO markedly increased mRNA expression levels of antioxidant genes including ferritin (FT), thioredoxin (Trx), GPX, glutathione S-transferase (GST) and catalase (CAT) and decreased peroxiredoxin (Prx) expression, in which expression of GPX and Prx were increased owing to MI supplementation. Therefore, it suggested that dietary OFO stimulated growth performance, but also induced oxidative stress and caused impairment to hepatopancreas in L. vannamei. The negative impact brought about by OFO was partially mitigated by dietary MI supplementation.

Effects of dietary myo-inositol on growth, chemical composition and plasma chemistry of Amur sturgeon Acipenser schrenckii

The present study was conducted to demonstrate the dietary myo-inositol requirement and its effects on the growth, proximate composition and blood chemistry of Amur sturgeon (Acipenser schrenckii). Triplicate groups of 30 fish (initial weight 11.90 ± 0.12 g) were fed different diets containing graded levels of myo-inositol (28.75, 127.83, 343.83, 565.81, 738.15 and 936.28 mg kg−1) until satiation for 56 days. The fish were weighed after a 24-h fast, and six fish were used for whole body composition analysis. Further, the liver and muscle were sampled from another six fish for lipid analysis. The blood and liver were sampled from the remaining six fish for haematology and fatty acid analysis. The weight gain of fish increased with myo-inositol content, from the 28.75- to 343.83-mg kg−1 myo-inositol treatment groups, and then stabilised. The liver lipid content and hepatosomatic index decreased significantly from 21.91 to 19.14% and from 3.20 to 2.76% with increased dietary myo-inositol supplementation, respectively. The whole body lipid content generally decreased from 6.33 to 5.55%. The content of liver-saturated fatty acids decreased significantly (28.13%) in the 936.28-mg kg−1 treatment group. The content of plasma non-esterified fatty acids increased with the increase in dietary myo-inositol supplementation from 0.77 to 1.17 mmol L−1, whereas the content of triglycerides significantly decreased from 4.62 to 3.28 mmol L−1. In conclusion, the optimum myo-inositol requirement was found to be 336.1 mg kg−1, based on weight gain in a two-slope quadratic broken-line model.

Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: a randomized controlled trial

Objective: To test the hypothesis that dietary myo-inositol may improve insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk of this disorder.Design: A prospective, randomized, double-blind, placebo controlled clinical trial, pilot study.Participants: Non-obese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy.Intervention: Supplementation with myo-inositol or placebo during pregnancy.Main outcome measure: Development of GDM on a 75 g oral glucose tolerance test at 24–28 weeks’ gestation. Secondary outcome measures were increased in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia.Results: Thirty-six women were allocated to receive myo-inositol and 39 placebo. The incidence of GDM in mid-pregnancy was significantly reduced (p = 0.001) in women randomized to receive myo-inositol compared to placebo (relative risk 0.127). Women randomized to receive myo-inositol also required less insulin therapy, delivered at a later gestational age, had significantly smaller babies with fewer episodes of neonatal hypoglycemia.Conclusions: Myo-inositol supplementation in pregnancy reduced the incidence of GDM in women at high risk of this disorder. The reduction in incidence of GDM in the treatment arm was accompanied by improved outcomes.

Streptozotocin 糖尿病ラットの embryogenesis における myo-inositol 添加の効果

Streptozotocin 糖尿病ラットの embryogenesis における myo-inositol 添加の効果

Dietarymyo-inositol requirement for Olive flounder,Paralichthys olivaceus(Temminch et Schlegel)

This study was aimed at examining the essentiality and requirement of inositol for Olive flounder, Paralichthys olivaceus. Six casein–gelatin-based semi-purified diets were formulated to contain five different levels of myo-inositol (MI) (designated as M0, M0+, M200, M400, M800 and M1600 for 0, 0+antibiotic, 200, 400, 800 and 1600 mg kg−1 respectively). After 20 weeks of a long-term feeding trial, fish (initial body weight, 10 g) fed the M800 diet showed significantly increased growth performances and survival. Liver lipid concentration tended to decrease as the dietary MI increased, although there was no significant difference among all treatments. Polyunsaturated fatty acid in the liver of the fish fed the diets containing high levels (M1600) of MI was significantly increased. Hepatic inositol concentration of the fish was significantly increased by dietary MI supplementation. The intestinal biosynthesis of inositol by microflora seemed to be insufficient to prevent growth retardation in juvenile Olive flounder. The optimum level of dietary MI for juvenile Olive flounder was found to be 617 mg kg−1 based on weight gain in a broken-line regression model. This finding indicates that MI supplementation is required at a concentration of at least 617 mg kg−1 to maximize the growth performances and to prevent abnormal lipid metabolism.

Dietary myo-inositol therapy in hyperglycemia-induced embryopathy.

Dysmorphogenesis in diabetic mothers occurs more frequently than in the general population. This phenomenon is believed to be caused by the teratogenic effects of metabolic fuel mixtures with associated membrane injury and aberrations in the biochemical constituents. The present experiment was designed to determine: 1) if hyperglycemia-induced membrane injury is associated with intracellular and/or extracellular lipid disturbances; 2) if supplemental myo-inositol therapy prevents hyperglycemia-induced embryopathy; 3) if a correlation exists between dietary myo-inositol, serum and tissue levels of myo-inositol, and conceptus development; and 4) the cellular content of arachidonic acid following myo-inositol supplementation. Sixty-five female Sprague-Dawley rats were mated, and divided into three groups. One group was nondiabetic normal controls, and two groups had diabetes experimentally induced with streptozotocin. Of the diabetic groups, one received a normal diet, while the other received a myo-inositol-supplemented diet during the period of organogenesis. Blood samples were collected on days 0 and 12 of pregnancy. Embryos and yolk sacs were analyzed for myo-inositol and arachidonic acid levels, using mass spectrochromatography. Dietary myo-inositol supplementation of diabetic mothers resulted in a significant decrease in the incidence of neural tube defects when compared with diabetics not receiving supplements (9.5 vs. 20.4%; P < 0.05). This protective effect was incomplete, based on the incidence observed in the nondiabetic controls (9.5 vs. 3.8%; P < 0.05). The myo-inositol embryonic tissue levels in the diabetic group which had been fed a regular diet without supplementation were significantly lower than in the nondiabetic group. Dietary therapy successfully restored myo-inositol levels in the yolk sacs, as suggested by similar tissue levels in diabetics receiving myo-inositol supplementation and normal controls (18.7 +/- 1.3 vs. 19.1 +/- 2.0 ng/mg; P = ns). Dietary therapy, however, failed to restore myo-inositol levels in the embryos, suggesting hyperglycemia-induced faulty transport of nutrients from the yolk sac to the embryo. No correlation was noted between maternal blood levels of myo-inositol, with or without supplementation, and the clinical outcome. Tissue arachidonic acid levels were markedly reduced in the conceptuses of diabetic mothers with (0.4 +/- 0.1 micrograms/mg) or without (0.25 +/- 0.08 micrograms/mg) myo-inositol supplementation when compared to the nondiabetic controls (3.33 +/- 0.24 micrograms/mg). These data demonstrate that diabetes-induced embryopathy is associated with a deficiency state in both myo-inositol and arachidonic acid. The myo-inositol deficiency is not demonstrated at the serum level, but rather at the tissue level, suggesting a paracrine action. Dietary supplementation of myo-inositol is associated with an increase in tissue myo-inositol levels and a decrease in malformations. This therapy holds promise for use as a dietary prophylaxis against diabetic embryopathy.

Dietary intake of myo-inositol and neural tube defects in offspring of diabetic rats

OBJECTIVE: Embryopathy in diabetic mothers occurs at a rate four to five times higher than that observed in the general population. The current investigation was undertaken to assess the use of dietary myo-inositol supplementation as a pharmacologic prophylaxis to obviate the teratogenic effects of hyperglycemia in an in vivo study. STUDY DESIGN: Seventy Sprague-Dawley rats were mated and after conception were randomly divided into five groups: one group was nondiabetic normal controls and four groups had diabetes experimentally induced with streptozotocin. Of the diabetic groups, one received the usual diet, whereas the others received, respectively, 0.08, 0.16, and 0.5 mg/day supplemental myo-inositol orally. RESULTS: With the myo-inositol supplementation (0.08 mg/day), the incidence of neural tube defects was significantly reduced from 20.4% to 9.5% ( p < 0.01). The most effective dosage of myo-inositol was 0.08 mg/day. Increasing the dose of myo-inositol beyond that level did not significantly reduce the rate of neural tube defects. However, the resorption rate was increased to 29.8%. CONCLUSION: These data demonstrate that myo-inositol supplementation reduces the incidence of diabetic embryopathy and may serve as a pharmacologic prophylaxis against diabetes-induced congenital malformations.(Am J Obstet Gynecol 1997;176:536-9.)

Supplemental myo-inositol prevents L-fucose-induced diabetic neuropathy.

Nerve myo-inositol depletion, which has been implicated in the pathogenesis of acute experimental diabetic neuropathy, can be reproduced in normal rats by feeding diets enriched in L-fucose, a competitive inhibitor of sodium-dependent myo-inositol transport. Previously, we reported that L-fucose feeding for 6 weeks reproduces the effect of experimental diabetes on nerve Na+-K+-ATPase activity and conduction velocity, which can be prevented by simultaneous dietary myo-inositol supplementation. To further validate this model of myo-inositol depletion, we examined the effects of long-term (24-week) L-fucose feeding and dietary myo-inositol supplementation on nerve Na+-K+-ATPase, nerve conduction velocity, and myelinated nerve fiber pathology. After 24 weeks of L-fucose enriched (10 or 20%) diets, nerve myo-inositol levels and Na+-K+-ATPase activity decreased significantly (P < 0.05) and were associated with a 25-30% reduction in nerve conduction velocity, all of which were completely prevented by 1% dietary myo-inositol. Twenty percent L-fucose diet resulted in significant axonal atrophy, paranodal swelling (P < 0.001), and paranodal demyelination (P < 0.005), without increasing Wallerian degeneration or nerve fiber loss, a pattern qualitatively similar to that seen in early murine diabetic neuropathy. Dietary myo-inositol supplementation prevented these structural changes and increased nodal remyelination, supporting a role of myo-inositol depletion in the genesis of early diabetic neuropathy. The L-fucose model system may therefore serve as an experimental tool to elucidate the pathophysiological role of isolated myo-inositol depletion and its consequences in the multifactorial pathogenesis of diabetic neuropathy.

Dietary myo-inositol supplementation does not prevent retinal and glomerular vascular structural changes in chronically diabetic rats

To assess effects of dietary myo-inositol supplementation on diabetes-induced vascular structural lesions, diabetes was induced in Sprague-Dawley rats with streptozotocin; one-third of these rats was fed a 2% myo-inositol diet for 9 months, one-third was left untreated for 5 months then treated with myo-inositol for the last 4 months, and one-third was untreated for the entire 9 months. Controls included untreated and myo-inositol-treated groups. Weight gain was impaired and plasma glucose, glycosylated hemoglobin, food consumption, urine volume, and albuminuria were increased significantly in diabetic versus age-matched control rats. Plasma myo-inositol levels were increased approximately fivefold in controls and approximately six- to eightfold in diabetic rats treated with myo-inositol. In general, myo-inositol did not affect any of the above parameters in control or diabetic rats. Retinal capillary basement membrane width (CBMW) was increased significantly (∼50% versus controls) after 9 months of diabetes. In the control group myo-inositol increased CBMW to the level of untreated diabetic rats; myo-inositol had no effect on CBMW in each diabetic group. The number of retinal capillaries containing pericyte nuclei and pericyte capillary coverage were increased in untreated as well as myo-inositol-treated diabetic rats and in the myo-inositol-treated control group. Glomerular CBMW was increased after 5 and 9 months of diabetes versus age-matched controls, and was increased even more by myo-inositol. Mesangial fractional volume of the glomerulus was increased 36% by diabetes and was decreased slightly but significantly by myo-inositol. These results indicate that diets supplemented with 2% myo-inositol (1) cause capillary basement membrane (CBM) thickening and pericyte changes in retinal capillaries of normal rats, (2) are ineffective in preventing or reversing diabetes-induced retinal CBM thickening, and (3) cause further thickening of glomerular CBM in diabetic rats.

Diminished specific activity of cytosolic protein kinase C in sciatic nerve of streptozocin-induced diabetic rats and its correction by dietary myo-inositol.

The impaired Na(+)-K(+)-ATPase activity in peripheral nerve from diabetic rats is prevented by dietary myo-inositol (MI) supplementation in vivo and corrected by protein kinase C (PKC) agonists in vitro, suggesting that PKC may mediate the effects of nerve MI depletion on Na(+)-K(+)-ATPase activity. However, little is known about the effect of diabetes on PKC activity or peptide in rat peripheral nerve. Therefore, the effect of streptozocin-induced diabetes and dietary MI supplementation on the activity and distribution of PKC in rat sciatic nerve homogenates and cytosolic and particulate fractions was explored with histone phosphorylation assay and Western-blot analysis. PKC activity but not peptide was selectively decreased in the cytosolic fraction by streptozocin-induced diabetes, and this abnormality was partially corrected by dietary MI supplementation. These results suggest that altered MI metabolism may affect nerve PKC specific activity, and this alteration may play a role in reduced Na(+)-K(+)-ATPase activity and blunted regenerative response in diabetic nerve.