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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Vydané v:Translational psychiatry Ročník 12; číslo 1; s. 350 - 8
Hlavní autori: Campbell, Iain H., Campbell, Harry, Smith, Daniel J.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 29.08.2022
Nature Publishing Group
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13/95
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692/699/476/1333
82/58
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Behavioral Sciences
Biological Psychology
Bipolar disorder
Extracellular vesicles
Insulin
Kinases
Lithium
Medicine
Medicine & Public Health
Neurosciences
Perspective
Pharmacotherapy
Phosphates
Psychiatry
ISSN:2158-3188, 2158-3188
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Shrnutí: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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ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-022-02122-6