Elsevier

Biochimie

Volume 95, Issue 10, October 2013, Pages 1811-1827
Biochimie

Review
Potential role and therapeutic interests of myo-inositol in metabolic diseases

https://doi.org/10.1016/j.biochi.2013.05.011Get rights and content

Highlights

  • Some inositol isomers and derivatives display insulin-mimetic activities.

  • Abnormalities in inositol metabolism are associated with insulin-resistance.

  • myo-Inositol dietary supplement corrects intracellular myo-inositol deficiency.

  • myo-Inositol dietary supplement improves insulin sensitivity.

Abstract

Several inositol isomers and in particular myo-inositol (MI) and D-chiro-inositol (DCI), were shown to possess insulin-mimetic properties and to be efficient in lowering post-prandial blood glucose. In addition, abnormalities in inositol metabolism are associated with insulin resistance and with long term microvascular complications of diabetes, supporting a role of inositol or its derivatives in glucose metabolism. The aim of this review is to focus on the potential benefits of a dietary supplement of myo-inositol, by far the most common inositol isomer in foodstuffs, in human disorders associated with insulin resistance (polycystic ovary syndrome, gestational diabetes mellitus or metabolic syndrome) or in prevention or treatment of some diabetic complications (neuropathy, nephropathy, cataract). The relevance of such a nutritional strategy will be discussed for each context on the basis of the clinical and/or animal studies. The dietary sources of myo-inositol and its metabolism from its dietary uptake to its renal excretion will be also covered in this review. Finally, the actual insights into inositol insulin-sensitizing effects will be addressed and in particular the possible role of inositol glycans as insulin second messengers.

Introduction

myo-Inositol is a cyclitol naturally present in animal and plant cells, either in its free form or as a bound-component of phospholipids or inositol phosphate derivatives. It plays an important role in various cellular processes, as the structural basis for secondary messengers in eukaryotic cells, and in particular as inositol triphosphates (IP3), phosphatidylinositol phosphate lipids (PIP2/PIP3) and possibly inositol glycans. For this reason, myo-inositol is essential or important for the smooth running of a wide range of cell functions, including cell growth and survival [1], development and function of peripheral nerves [2], osteogenesis [3] and reproduction [4], [5], [6], [7], [8], [9] (See Fig. 1). myo-Inositol and d-chiro-inositol, another inositol isomer, could be also implicated in glucose homeostasis since abnormalities in their metabolism were associated to insulin-resistance and long-term diabetes microvascular complications in diabetic subjects. Furthermore, given as dietary supplements, both myo- and d-chiro-inositol showed insulin-mimetic effects in several animal models of insulin resistance [10], [11], [12] and in women with polycystic ovary syndrome [13], a metabolic and endocrine disorder associated with insulin resistance.

The aim of this review is to compile and discuss the results of the randomized controlled trials that tested the potential benefit of a dietary myo-inositol supplement in contexts of insulin-resistance or long-term diabetic complications. As an introduction and to further discuss the therapeutic interest of a myo-inositol supplement in those contexts, the dietary sources of myo-inositol, its metabolism from its oral intake to its catabolism by the kidney, and the abnormalities in inositol metabolism associated with insulin-resistance will be addressed. Finally, the putative and actually unclearly defined mechanisms of action of inositol derivatives as insulin sensitizers will be discussed on the basis of animal and clinical studies.

Section snippets

Biological forms and dietary sources

Inositol or cyclohexane-1,2,3,4,5,6-hexol is a polyol existing under nine stereoisomeric forms depending on the spatial orientation of its six hydroxyl groups (Fig. 2). myo-Inositol, or cis-1,2,3,5-trans-4,6-cyclohexanehexol, is the predominant isomeric form of inositol that we can find in nature and in our food. myo-Inositol was once considered to belong to the vitamin B family, however, because it is produced in sufficient amount by the human body from d-glucose, it is no more regarded as an

Digestion and absorption

myo-Inositol from phytic acid can be released in the gut of monogastric animals by the enzymes phytases, which occurs in the intestinal mucosa. Phytases (myo-inositol hexaphosphate phosphohydrolase, EC 3.1.3.8 and EC 3.1.3.26) are found in plants, microorganisms and in animal tissues [15]. These enzymes are capable of releasing free inositol, orthophosphate, and intermediary products including the mono-, di-, tri-, tetra- and penta-phosphate forms of inositol. Much of the ingested inositol

Inositol metabolism abnormalities associated with insulin resistance

MI and DCI are involved in an array of cellular functions and abnormalities in their metabolism have been involved in the development of several diseases states (e.g. Bipolar, Panic and Obsessive Compulsive Disorders, Depression, Alzheimer's Disease) and in particular in the development of insulin resistance and diabetic complications. Indeed, in primary sites for the development of diabetic microvascular complications (kidney, sciatic nerve, retina and lens) a concomitant depletion of

Polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting 5–10% of women in reproductive age and characterized by hyperandrogensim, polycystic ovaries and ovulatory dysfunction. According to the 2003 Rotterdam Consensus Criteria, PCOS can be diagnosed after exclusion of other conditions that causes hyperandrogenism and if at least two of the following three criteria are present: chronic oligo- or anovulation (manifesting as oligoamenorrhea or amenorrhea), elevated

MI supplementation effects on diabetic complications

In diabetes, tissues likely to develop long-term microvascular complications (kidney, sciatic nerve, lens and retina) are depleted in MI and this MI intracellular deficiency could play a pivotal role in the development and progression of these complications. Restoring MI intracellular levels with dietary MI supplement could then be a suitable strategy to prevent or delay the development of diabetic neuropathy, nephropathy or retinopathy.

Concluding remarks

myo-Inositol is a polyol naturally present in eukaryotic cells and is a component of numerous biological molecules, including second messengers like IP3, PIP2/PIP3 and IPGs which makes it essential for numerous biological processes. Abnormalities in its metabolism are associated to pathological states and in particular, MI intracellular deficiency in sciatic nerve, kidney, lens and retina of diabetic subjects probably contribute to the development or aggravation of some diabetes complications

Disclosure

The authors declare no conflict of interest.

Acknowledgments

M.L. Croze is supported by a grant from the French «Ministère de la Recherche et de la Technologie». The authors gratefully acknowledge Pr Michel Guichardant (INSERM U1060, CarMeN, INSA-Lyon) for fruitful discussions.

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