Insulin and IGF-1 enhance the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin pathway.

Details

Serval ID
serval:BIB_C70A15198A89
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Insulin and IGF-1 enhance the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin pathway.
Journal
European Journal of Neuroscience
Author(s)
Chenal J., Pierre K., Pellerin L.
ISSN
1460-9568
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
27
Number
1
Pages
53-65
Language
english
Abstract
MCT2 is the main neuronal monocarboxylate transporter essential for facilitating lactate and ketone body utilization as energy substrates. Our study reveals that treatment of cultured cortical neurons with insulin and IGF-1 led to a striking enhancement of MCT2 immunoreactivity in a time- and concentration-dependent manner. Surprisingly, neither insulin nor IGF-1 affected MCT2 mRNA expression, suggesting that regulation of MCT2 protein expression occurs at the translational rather than the transcriptional level. Investigation of the putative signalling pathways leading to translation activation revealed that insulin and IGF-1 induced p44- and p42 MAPK, Akt and mTOR phosphorylation. S6 ribosomal protein, a component of the translational machinery, was also strongly activated by insulin and IGF-1. Phosphorylation of p44- and p42 MAPK was blocked by the MEK inhibitor PD98058, while Akt phosphorylation was abolished by the PI3K inhibitor LY294002. Phosphorylation of mTOR and S6 was blocked by the mTOR inhibitor rapamycin. In parallel, it was observed that LY294002 and rapamycin almost completely blocked the effects of insulin and IGF-1 on MCT2 protein expression, whereas PD98059 and SB202190 (a p38K inhibitor) had no effect on insulin-induced MCT2 expression and only a slight effect on IGF-1-induced MCT2 expression. At the subcellular level, a significant increase in MCT2 protein expression within an intracellular pool was observed while no change at the cell surface was apparent. As insulin and IGF-1 are involved in synaptic plasticity, their effect on MCT2 protein expression via an activation of the PI3K-Akt-mTOR-S6K pathway might contribute to the preparation of neurons for enhanced use of nonglucose energy substrates following altered synaptic efficacy.
Keywords
Animals, Cells, Cultured, Cerebral Cortex, Enzyme Activation, Gene Expression, Immunosuppressive Agents, Insulin, Insulin-Like Growth Factor I, Mice, Models, Biological, Monocarboxylic Acid Transporters, Neurons, Proto-Oncogene Proteins c-akt, Signal Transduction, Sirolimus, Transfection
Pubmed
Web of science
Create date
29/01/2009 22:14
Last modification date
20/08/2019 15:42
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