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Study of the insulin-sensitizing effect of myo-inositol in mouse : Evaluation of the nutritional interest of a myo-inositol supplementation

Abstract : Insulin resistance is the first step in the development of type 2 diabetes so finding insulin-sensitizing strategies is challenging for scientists. Some inositol isomers or derivatives have been reported to exert insulin-mimetic activity. myo-Inositol being the most abundant stereoisomeric form of inositol in foodstuffs, we tested its insulin-mimetic potential in the long term and as a nutritional strategy for insulin resistance prevention and/or treatment. This study demonstrates that chronic myo-inositol treatment improves insulin sensitivity, reduces white adipose tissue accretion and improves mice survival mice to paraquat challenge. The insulin-sensitizing effect seems to be related to a direct effect on insulin signaling pathway. Reduction in adipose tissue mass also probably contribute to the long term effect of myo-inositol on insulin sensitivity. Myo-Inositol supplementation also improved insulin sensitivity and reduced white adipose tissue deposition in mice fed a high fat diet, but did not prevent insulin-resistance or obesity development. On one year-old mice with established obesity and altered glycemic control, myo-inositol supplementation showed no beneficial effect. myo-Inositol apparently acts on adipose tissue through reduction of de novo lipogenesis rather than stimulation of lipolysis. This may explain the lack or loss of myo-inositol efficiency in reducing adipose tissue mass in contexts of already well-established obesity (old mice) or reduced de novo lipogenesis (high fat diet feeding). Generation of inositol glycan putative insulin second messengers is probably reduced in context of insulin resistance which may explain the reduced effect of myo-inositol in both obese mice models. Moreover, myo-Inositol did not prevent lipotoxicity and so the associated insulin-resistance in high fat diet fed mice. In conclusion, myo-inositol alone and/or in a context of overnutrition is not a suitable strategy for the prevention or treatment of insulin resistance. Combining it with other insulin sentitizing strategies may however potentiate their action and help reducing insulin-sensitizing drugs use.
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  • HAL Id : tel-01081062, version 1

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Marine Croze. Study of the insulin-sensitizing effect of myo-inositol in mouse : Evaluation of the nutritional interest of a myo-inositol supplementation. Biochemistry, Molecular Biology. INSA de Lyon, 2013. English. ⟨NNT : 2013ISAL0139⟩. ⟨tel-01081062⟩

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