Medina-Vera, DinaNavarro, Juan AntonioTovar, RubénRosell-Valle, CristinaGutiérrez-Adan, AlfonsoLedesma, Juan CarlosSanjuan, CarlosPavón, Francisco JavierBaixeras, ElenaRodríguez de Fonseca, FernandoDecara, Juan2022-07-062022-07-062021-06-30Medina-Vera D, Navarro JA, Tovar R, Rosell-Valle C, Gutiérrez-Adan A, Ledesma JC, et al. J. Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol. Nutrients. 2021 Jun 30;13(7):2268http://hdl.handle.net/10668/3750D-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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/InositolD-PinitolInsulin resistanceHypothalamusPI3K/Akt pathwayResistencia a la insulinaHipotálamoFosfatidilinositol 3-quinasasProteínas proto-oncogénicas c-aktRatasMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Routes::Administration, OralMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose::Blood GlucoseMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Enzyme ActivationMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::Proglucagon::GlucagonMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::HomeostasisMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::HypothalamusMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::Sugar Alcohols::InositolMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::InsulinsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance::Insulin ResistanceMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Somatomedins::Insulin-Like Growth Factor IMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Phosphatidylinositol 3-Kinases::Phosphatidylinositol 3-KinaseMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Organic Chemistry Phenomena::Organic Chemistry Processes::PhosphorylationMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, WistarMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal TransductionMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins::Proto-Oncogene Proteins c-aktMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Ratsresearch article34209137open access10.3390/nu130722682072-6643PMC8308282