The Nutritional Significance, Metabolism, and Function of myo-Inositol and Phosphatidylinositol in Health and Disease

Holub, Bruce J.

doi:10.1007/978-1-4613-9934-6_5

Cited by 74 publications

(46 citation statements)

References 225 publications

(162 reference statements)

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“…In agreement with this conclusion, the dietary requirement for MI was first established by using gerbils, linking an MI-free diet to pathological conditions such as lipodystrophy of the small intestine, presumably because of failure in lipid absorption through chylomicrons (7,18), and dysregulation of triglyceride metabolism in the liver (19). Using purified BBMv, we now demonstrate through extensive characterization that, in the rat, SMIT2 is present in the apical membranes of enterocytes and is responsible for all MI absorption.…”

supporting

confidence: 66%

SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine

Aouameur¹,

Cal²,

Bissonnette³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Aouameur R, Da Cal S, Bissonnette P, Coady MJ, Lapointe J-Y. SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine. Am J Physiol Gastrointest Liver Physiol 293: G1300-G1307, 2007. First published October 11, 2007; doi:10.1152/ajpgi.00422.2007.-This study presents the characterization of myo-inositol (MI) uptake in rat intestine as evaluated by use of purified membrane preparations. Three secondary active MI cotransporters have been identified; two are Na ϩ coupled (SMIT1 and SMIT2) and one is H ϩ coupled (HMIT). Through inhibition studies using selective substrates such as D-chiro-inositol (DCI, specific for SMIT2) and L-fucose (specific for SMIT1), we show that SMIT2 is exclusively responsible for apical MI transport in rat intestine; rabbit intestine appears to lack apical transport of MI. Other sugar transport systems known to be present in apical membranes, such as SGLT1 or GLUT5, lacked any significant contribution to MI uptake. Functional analysis of rat SMIT2 activity, via electrophysiological studies in Xenopus oocytes, demonstrated similarities to the activities of SMIT2 from other species (rabbit and human) displaying high affinities for MI (0.150 Ϯ 0.040 mM), DCI (0.31 Ϯ 0.06 mM), and phlorizin (Pz; 0.016 Ϯ 0.007 mM); low affinity for glucose (36 Ϯ 7 mM); and no affinity for L-fucose. Although these functional characteristics essentially confirmed those found in rat intestinal apical membranes, a unique discrepancy was seen between the two systems studied in that the affinity constant for glucose was ϳ40-fold lower in vesicles (Ki ϭ 0.94 Ϯ 0.35 mM) than in oocytes. Finally, the transport system responsible for the basolateral efflux transporter of glucose in intestine, GLUT2, did not mediate any significant radiolabeled MI uptake in oocytes, indicating that this transport system does not participate in the basolateral exit of MI from small intestine. brush border; glucose; transport; oocytes; phlorizin THE PHYSIOLOGICAL IMPORTANCE of myo-inositol (MI) is generally considered to reflect its role in signal transduction as a precursor to phosphoinositides and inositol phosphates. In addition, MI acts as a "compatible osmolyte" in specific tissues, such as brain and kidney medulla, where variations in milieu osmolarity may threaten normal cell function. In response to an increase in osmolarity, intracellular MI concentration may rise up to 500-fold above its plasma concentration of ϳ30 M (9, 11, 12), where it prevents the accumulation effects of high ionic concentrations, which leads to DNA degradation (11a). This has been well documented in brain where conditions such as trauma (30), edema and hypernatremia (26,27,38) have been shown to increase MI levels. To reach such high intracellular concentrations, secondary active transport systems are required for MI.

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supporting

confidence: 66%

SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine

Aouameur¹,

Cal²,

Bissonnette³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…This 'lipotropic' (Holub, 1982;Wells, 1989) mechanism may be due to a very low solubility of inositol in the phospholipid layers of the membrane, which allows a limited diffusion across the plasma membrane. The magnitude of the sodium-independent uptake in cleavage stage embryos at physiological concentrations of inositol was probably over-estimated due to the presence of the sodium salts of pyruvate (0.5 mmol l −1 ) and some amino acids in the sodium minus incubation medium.…”

Section: Discussionmentioning

confidence: 99%

Inositol transport in preimplantation rabbit embryos: effects of embryo stage, sodium, osmolality and metabolic inhibitors

Warner¹,

Conlon²,

Kane³

2003

Reproduction

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The preimplantation period in the rabbit consists of a 3 day cleavage stage during which the number of cells increases with little change in embryo size, followed by a 3-4 day blastocyst stage during which the inner cell mass, the blastocoel and the trophectodermal layer are formed and the embryo grows rapidly in size and protein content. This study used Inositol uptake increased to 0.58 pmol per embryo per h for early blastocysts (day 4) and 23.7 pmol for late blastocysts (day 6). There was a significant linear relationship between inositol uptake and blastocyst diameter and surface area. Efflux of inositol from early morulae was minimal (about 1.25% of embryo content per h), whereas efflux from mid-blastocysts (day 5) was much greater (about 15.6% of embryo content per h). Efflux of inositol from both early morulae and mid-blastocysts was increased by decreasing the osmolality of the incubation medium. Varying the osmolality had no effect on inositol uptake up to 2 h. Inositol uptake was dependent on sodium in cleavagestage embryos but independent of sodium in blastocyst stages. In early morulae, inositol uptake was inhibited by glucose and the sodium-dependent hexose transport inhibitor, phloridzin, but not by the facilitated transport inhibitor, phloretin. Inositol uptake in early morulae was saturable; estimates of 0.227 and 0.288 pmol per morula per h for V max and 0.045 and 0.038 mol l −1 for K m were obtained for sodium-dependent transport in two separate experiments. All of these results are consistent with the hypothesis that transport in cleavage stages occurs via a sodium myo-inositol transporter (SMIT) protein. Uptake in blastocysts was non-saturable. Uptake into blastocysts appeared to take place by a transcellular rather than a paracellular route.

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“…Animals kept on inositol-free diets developed alopecia and "fatty liver" (reviewed in Ref. 642). Subsequently, it was found that mammalian cells required myo-inositol to grow properly in culture (394).…”

Section: Historical Overviewmentioning

confidence: 99%

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Balla

2013

Physiological Reviews

1,396

1,655

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Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.

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The Nutritional Significance, Metabolism, and Function of myo-Inositol and Phosphatidylinositol in Health and Disease

Cited by 74 publications

References 225 publications

SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine

SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine

Inositol transport in preimplantation rabbit embryos: effects of embryo stage, sodium, osmolality and metabolic inhibitors

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

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