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Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder

In this paper, we propose that lithium may exert its therapeutic effect in bipolar disorder by acting on insulin signaling pathways. Specifically, we assess the importance of the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) insulin signaling pathway and we assess how the action of lithi...

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Autores principales: Campbell, Iain H., Campbell, Harry, Smith, Daniel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424309/
https://www.ncbi.nlm.nih.gov/pubmed/36038539
http://dx.doi.org/10.1038/s41398-022-02122-6
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author Campbell, Iain H.
Campbell, Harry
Smith, Daniel J.
author_facet Campbell, Iain H.
Campbell, Harry
Smith, Daniel J.
author_sort Campbell, Iain H.
collection PubMed
description In this paper, we propose that lithium may exert its therapeutic effect in bipolar disorder by acting on insulin signaling pathways. Specifically, we assess the importance of the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) insulin signaling pathway and we assess how the action of lithium on both glycogen synthase kinase-3 (GSK3) and the phosphatidylinositol cycle may lead to mood stabilization mediated by PI3K/Akt insulin signaling. We also highlight evidence that several other actions of lithium (including effects on Akt, Protein kinase C (PKC), and sodium myo-inositol transporters) are putative mediators of insulin signaling. This novel mode of action of lithium is consistent with an emerging consensus that energy dysregulation represents a core deficit in bipolar disorder. It may also provide context for the significant co-morbidity between bipolar disorder, type 2 diabetes, and other forms of metabolic illness characterized by impaired glucose metabolism. It is suggested that developments in assessing neuronal insulin signaling using extracellular vesicles would allow for this hypothesis to be tested in bipolar disorder patients.
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spelling pubmed-94243092022-08-31 Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder Campbell, Iain H. Campbell, Harry Smith, Daniel J. Transl Psychiatry Perspective In this paper, we propose that lithium may exert its therapeutic effect in bipolar disorder by acting on insulin signaling pathways. Specifically, we assess the importance of the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) insulin signaling pathway and we assess how the action of lithium on both glycogen synthase kinase-3 (GSK3) and the phosphatidylinositol cycle may lead to mood stabilization mediated by PI3K/Akt insulin signaling. We also highlight evidence that several other actions of lithium (including effects on Akt, Protein kinase C (PKC), and sodium myo-inositol transporters) are putative mediators of insulin signaling. This novel mode of action of lithium is consistent with an emerging consensus that energy dysregulation represents a core deficit in bipolar disorder. It may also provide context for the significant co-morbidity between bipolar disorder, type 2 diabetes, and other forms of metabolic illness characterized by impaired glucose metabolism. It is suggested that developments in assessing neuronal insulin signaling using extracellular vesicles would allow for this hypothesis to be tested in bipolar disorder patients. Nature Publishing Group UK 2022-08-29 /pmc/articles/PMC9424309/ /pubmed/36038539 http://dx.doi.org/10.1038/s41398-022-02122-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Perspective
Campbell, Iain H.
Campbell, Harry
Smith, Daniel J.
Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder
title Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder
title_full Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder
title_fullStr Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder
title_full_unstemmed Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder
title_short Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder
title_sort insulin signaling as a therapeutic mechanism of lithium in bipolar disorder
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424309/
https://www.ncbi.nlm.nih.gov/pubmed/36038539
http://dx.doi.org/10.1038/s41398-022-02122-6
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