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

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.

Keywords: 1-d-myo-inositol-phosphate synthase; 5′ AMP-activated protein kinase; AC; ACC; AGEs; AMP; AMPK; AUC; BMI; Body Mass Index; CDP-DAG; D-chiro-inositol; DCI; Diabetes; Diabetic neuropathy; ECM; FA; FSH; G3PAT; GFR; GK; GLUT-4; GMD; GPI; GS; GSK3; Goto Kakizaki (rat); H(+)/myo-inositol transporter; HDL; HK; HMIT; HOMA-IR; IMPase; INS-2; IPG; IPs; IR; IRS; Inositol; Insulin resistance; LD50; LDL; LH; LysoPI; MI; MIOX; MIPS; MNCV; MetS; Metabolic syndrome; OGTT; PCOS; PDH; PDHP; PDK; PI; PI3K; PIPs; PKA; PKB; PKC; PLC; PLD; PP-InsPs; PP2Cα; Polycystic ovary syndrome; Protein Kinase B; RCT; SHBG; SHR; SMIT1/2; STZ; Sex Hormon Binding Globulin; acetyl-coenzyme A carboxylase; adenosine monophosphate; adenylyl cyclase; advanced glycation end products; area under the curve; cAMP; cyclic AMP; cyclic AMP-dependent protein kinase; cytidine diphosphate-diacylglycerol; extracellular matrix; folic acid; follicle-stimulating hormone; gestational diabetes mellitus; glomerular filtration rate; glucose transporter 4; glycerol-3-phosphate acyltransferase; glycogen synthase; glycogen synthase kinase 3; glycosyl phosphatidylinositol; hexokinase; high density lipoprotein; homeostasis model assessment of insulin resistance; inositol monophosphatase; inositol phosphates (including in particular: Ins-P: inositol monophosphate, IP3, inositol triphosphates, IP6, inositol hexakisphosphates or phytic acid); inositol phosphoglycan; insulin receptor; insulin receptor substrate(s); insulin second messenger with a 4-O-(2-amino-2-deoxy-beta-d-galactopyranosyl)-3-O-methyl-d-chiro-inositol structure; low density lipoprotein; luteinizing hormone; lysophosphatidylinositol; mTOR; mammalian target of rapamycin; median lethal dose; metabolic syndrome; motor nerve conduction velocity; myo-inositol; myo-inositol oxygenase; oral glucose tolerance test; phosphatidylinositol; phosphatidylinositol phosphate lipids (including PIP(2), phosphatidylinositol 4,5-bisphosphate and PIP(3), phosphatidylinositol (3,4,5)-trisphosphate); phosphatidylinositol-3-kinase(s); phosphoinositide-dependent kinase; phospholipase C; phospholipase D; phosphoprotein phosphatase 2C alpha; polycystic ovary syndrome; protein kinase C; pyrophosphate forms of inositol phosphates; pyruvate dehydrogenase; pyruvate dehydrogenase phosphatase; randomized controlled trial; sodium-dependant myo-inositol transporter 1/2; spontaneously hypertensive rat; streptozotocin.