Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.
This work was supported by grants from the following institutions: Ministerio de Economía y Competitividad, Gobierno de España (Grant RTC-2016-4983-1), EU-ERDF-Instituto de Salud Carlos III (Grant PI19/01577), and Consejería de Economía, Conocimiento y Universidad, Junta de Andalucía (Grant P18-TP-5194), Proyecto de Investigación en Salud, Consejería de Salud y Familias (PI-0139-2018). D.M-V. (FI20/00227) holds a “PFIS” predoctoral contract from the National System of Health, EU-ERDF-Instituto de Salud Carlos III