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 path...

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Bibliographic Details
Authors: Medina-Vera, Dina, Navarro, Juan Antonio, Tovar, Rubén, Rosell-Valle, Cristina, Gutiérrez-Adan, Alfonso, Ledesma, Juan Carlos, Sanjuan, Carlos, Pavón, Francisco Javier, Baixeras, Elena, Rodríguez de Fonseca, Fernando, Decara, Juan
Format: article
Publication Date:2021
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/18391
Online Access:http://hdl.handle.net/20.500.12105/18391
Access Level:Open access
Keyword:Inositol
D-Pinitol
Insulin resistance
Hypothalamus
PI3K/Akt pathway
Resistencia a la insulina
Hipotálamo
Fosfatidilinositol 3-quinasas
Proteínas proto-oncogénicas c-akt
Ratas
Administration, Oral
Animals
Blood Glucose
Enzyme Activation
Glucagon
Homeostasis
Insulins
Insulin Resistance
Insulin-Like Growth Factor I
Phosphatidylinositol 3-Kinase
Phosphorylation
Rats, Wistar
Signal Transduction
Proto-Oncogene Proteins c-akt
Rats
Description
Summary: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.