Urinary chiro-Inositol and myo-inositol Excretion is Elevated in the Diabetic db/db Mouse and Streptozotocin Diabetic Rat

J, Kawa; Przybylski, Roman; Taylor, Carla G.

doi:10.1177/153537020322800806

Cited by 45 publications

(47 citation statements)

References 21 publications

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“…[107] In a rat model of type 1 diabetes and a mouse model of type 2 diabetes the urinary excretion of D-chiro-inositol was much greater than in healthy rats and mice. [108] These studies contradict earlier work showing a lower urinary excretion (and lower muscle content) of D-chiro-inositol in non-insulin-dependent diabetics than in nondiabetics. [109] The transport into cells of D-chiro-inositol by SMIT2 is up-regulated by insulin so the increased urinary excretion of D-chiro-inositol in diabetics may be due to the lack of activity of SMIT2 consequent upon a shortage of insulin.…”

Section: D-chiro-inositol Diabetes Pregnancy and Polycystic Ovary Scontrasting

confidence: 64%

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

2015

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Cell signalling via inositol phosphates, eg the second messenger myo-inositol 1,4,5-trisphosphate, and phosphoinositides comprises a huge field of biology. Of 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, recently, neoand D-chiro-inositol hexakisphosphates were revealed in both terrestrial and aquatic ecosystems, 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, e.g. scyllo-inositol (neurodegenerative diseases), and D-chiro-inositol (diabetes). It is timely to consider exploration of roles and applications of "other" isomers and their derivatives, likely by exploiting techniques now well developed for the myo-series.

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Section: D-chiro-inositol Diabetes Pregnancy and Polycystic Ovary Scontrasting

confidence: 64%

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

2015

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“…Due to its role as a second messenger in the signal transduction processes, several clinical trials (10)(11)(12)(13)(14)(15)(16) have suggested a beneficial effect of inositol (myo-or chiro-) supplementation in improving ovarian function, hormone status and glucose homeostasis, with no reported side effects, For this reason, it may potentially be used on a population-wide level.…”

Section: Discussionmentioning

confidence: 99%

“…Abnormalities in myo-inositol and in D-chiro-inositol metabolism have been involved in the development of several diseases and in particular in the development of IR and diabetic complications (11,12).…”

Section: The Influence Of D-chiro-inositol and D-myo-inositol In Pregmentioning

confidence: 99%

The influence of D-chiro-inositol and D-myo-inositol in pregnant women with glucose intolerance

et al. 2017

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Abstract. The aim of the present study was to demonstrate that the use of inositol and folic acid from the first trimester of pregnancy, counteracts the onset of gestational diabetes mellitus (GDM) in women at risk, preserving the infants from macrosomia, hypoglycemia and preterm delivery. The authors collected data from the pregnant women at the laboratory (Unit of Cytogenic and Molecular Genetics), from January 2014 to April 2016, all with first trimester fasting plasma glucose (FPG) >92 mg/dl. A total of 40 women were treated with 250 mg/day D-chiro-inositol, 1.75 g/day D-myo-inositol, 12.5 mg/day zinc, 10 mg/day methylsulfonylmethane, 400 µg/day 5-methyltetrahydrofolic acid. The other 43 women (control group) were treated with only 400 µg/day folic acid. The primary outcome measure was the incidence of maternal GDM. The secondary outcome measures were the incidence of fetal macrosomia, preterm delivery and neonatal hypoglycemia. At the 24th week of pregnancy, the incidence of maternal GDM was recorded in 18 women in the control group and in 5 women in the treated group [relative risk (RR)=3.35; 95% confidence interval (CI)=1.37-8.17; P=0.0028). A significant difference was observed between treated and control groups in terms of risk of macrosomia. A total of seven infants in the control group, and two in the treated group, weighed >4,000 g (RR=5,12; 95% CI=1.21-21.68; P=0.0099). No significant difference was identified between two groups, regarding the other two secondary outcomes, neonatal hypoglycemia (RR=4.650; 95% CI= 0.57-38.11; P= 0.1086) and preterm delivery (RR=1.74; 95% CI=0.83-3.66; P=0.1301). The current study demonstrated the potential benefit of supplementation with the association of D-chiro-inositol and D-myo-inositol in pregnant 'at risk' women, with first trimester FPG >92 mg/dl, in preventing the onset of maternal GDM and macrosomia in newborns.

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“…In diabetes, the depletion of intracellular myo-inositol pools related to increased synthesis of sorbitol from glucose with accentuated AR activity in the renal medulla and increased urinary excretion of MI to maintain homeostasis inside the cell is described in ref. 34. Thus, the increased RSOR͞MIOX activity in the renal cortex in diabetes can be ascribed to the maintenance of homeostasis and osmoregulation in the kidney by catabolizing glucose intermediaries, e.g., myo-inositol.…”

Section: Discussionmentioning

confidence: 99%

Modulation of renal-specific oxidoreductase/ myo -inositol oxygenase by high-glucose ambience

Nayak¹,

Xie²,

Akagi³

et al. 2005

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

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Biological properties of renal-specific oxidoreductase (RSOR), characteristics of its promoter, and underlying mechanisms regulating its expression in diabetes were analyzed. RSOR expression, normally confined to the renal cortex, was markedly increased and extended into the outer medullary tubules in db͞db mice, a model of type 2 diabetes. Exposure of LLCPK cells to D-glucose resulted in a dose-dependent increase in RSOR expression and its enzymatic activity. The latter was related to one of the glycolytic enzymes, myo-inositol oxygenase. The increase in activity was in proportion to serum glucose concentration. The RSOR expression also increased in cells treated with various organic osmolytes, e.g., sorbitol, myoinositol, and glycerolphosphoryl-choline and H 2O2. Basal promoter activity was confined to ؊1,252 bp upstream of ATG, and it increased with the treatment of high glucose and osmolytes. EMSAs indicated an increased binding activity with osmotic-, carbohydrate-, and oxidant-response elements in cells treated with high glucose and was abolished by competitors. Supershifts, detected by anti-nuclear factor of activated T cells, and carbohydrate-response-element-binding protein established the binding specificity. Nuclear factor of activated T cells tonicityenhancer-binding protein and carbohydrate-response-elementbinding protein had increased nuclear expression in cells treated with high glucose. The activity of osmotic-response element exhibited a unique alternate binding pattern, as yet unreported in osmoregulatory genes. Data indicate that RSOR activity is modulated by diverse mechanisms, and it is endowed with dual properties to channel glucose intermediaries, characteristic of hepatic aldehyde reductases, and to maintain osmoregulation, a function of renal medullary genes, e.g., aldose reductase, in diabetes. diabetic nephropathy ͉ hyperglycemia ͉ osmoregulation D iabetic nephropathy is characterized by hyperplasia͞ hypertrophy of intrinsic renal cells and increased extracellular matrices (1). These changes are related to the increased cellular flux of glucose intermediaries (2), de novo synthesis of intra-and extracellular advanced glycation end products (3, 4), activation of protein kinase C (5, 6), increased expression of transforming growth factor-␤ (7), increased activity of GTP-binding and cell-cycle proteins (6,8), and generation of reactive oxygen species (9, 10), with consequential compromise in renal functions (11,12). Such complex interrelated cellular signaling events, also involving various forms of MAP͞ERK kinases and Smad proteins, have been defined mainly in glomerular cells (13,14); information relevant to the tubulointerstitial cells, although notably affected, is limited (15, 16). Conceivably, cellular changes in the tubulointerstitium parallel those in the glomerulus, with scarring and thickening of the basement membranes, and they correlate relatively better with the derangements in renal functional parameters (17, 18). Thus, much attention is warranted to the understanding of the...

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Urinary chiro-Inositol and myo-inositol Excretion is Elevated in the Diabetic db/db Mouse and Streptozotocin Diabetic Rat

Cited by 45 publications

References 21 publications

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

The influence of D-chiro-inositol and D-myo-inositol in pregnant women with glucose intolerance

Modulation of renal-specific oxidoreductase/ myo -inositol oxygenase by high-glucose ambience

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