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

Abstract

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.

d‐Pinitol promotes tau dephosphorylation through a cyclin‐dependent kinase 5 regulation mechanism: A new potential approach for tauopathies?

“…These data also point to a regional specificity of the actions of DPIN on both tau phosphorylation and brain insulin signalling. Thus, we did not detect changes in the hypothalamus nor in the temporal cortex of the Wistar rats treated with DPIN for 10 days (Figure S3), whereas we did observe a clear activation of PI3K/Akt signalling pathway in the hypothalamus after DPIN administration (Medina‐Vera et al, 2021).…”

Symbiotic microbes aid host adaptation by metabolizing a deterrent host pine carbohydrate d -pinitol in a beetle-fungus invasive complex

“…In recent years, d -pinitol has been used as a bioactive compound for many diseases, especially diabetes ( 29 , 30 , 56 ). Oral ingestion of d -pinitol significantly improves the insulin-glucose metabolic homeostasis of diabetic patients, streptozotocin-diabetic rats, and glucose-loaded mice ( 32 , 33 , 57 , 58 ). Further studies showed that d -pinitol acts through the phosphatidylinositol 3-kinase/protein kinase B ( PI3K / Akt ) pathway ( 57 , 59 ).…”

Semaphorin3F reduces vascular endothelial and smooth muscle cell PI3K activation and decreases neointimal plaque formation

“…PDGF-BB induces the synthetic phenotype in VSMCs via an extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI3K/AKT)-mediated pathway, resulting in reduced ACTA2 and SM22α activity (36), suggesting that PI3K activity maybe increased in Sema3f -/- VSMCs. Indeed, phospho-PI3K p85α (Tyr607), a marker of PI3K activity (37), was increased in vivo in lesional αSMA-positive Sema3f -/- VSMCs ( Sema3f +/+ : 39.8±4.7, n=3; Sema3f -/- : 63.9±2.0, n=5; phospho-PI3K expression (% of mature SMCs), p=0.001, Figure 5F), suggesting that SEMA3F-mediated modulation of PI3K activity may contribute to the pro-atherogenic VSMC phenotypes in Sema3f -/- mice.…”