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.
Highlights
To evaluate the insulin-mimetic actions of DPIN, we focus on the Phosphatidylinositol3-kinase (PI3K)/Protein Kinase B (Akt) signaling pathway (Figure 1B), which is part of the insulin cascade via Insulin Receptor Substrate 1 (IRS-1)
The oral administration of 500 mg/kg DPIN resulted in a rapid rise of DPIN in plasma (Figure 2A) that peaked at 120 min (p < 0.001) after its administration, which is rapidly cleared from thereafter (p < 0.05)
Insulin seninositols have been suggested for these purposes, no studies addressed impact of sitizers such as inositols have been suggested for these purposes, no studies adthese compounds on insulin signaling in the hypothalamus, the main brain center for metabolic dressed the impact of these compounds on DPIN
Summary
Inositols (1,2,3,4,5,6-cyclohexanehexol) can be differentiated depending on six hydroxyl groups configuration being D-Pinitol (DPIN) a methylated at the 3-position OH [1]. DPIN is existing by nature plant inositol derivates being a bioactive compound with insulinlike effect [2]. DPIN is present in pine trees, legumes, seeds, and flowers having one of the highest antioxidant activities of the inositols [3]. Inositols, including DPIN, can be found in mammalian as inositol glycans (IGs) [4], carbohydrates derived from glycolipids produced by insulin-sensitive cells in response to insulin treatment [5]. IGs were first identified in 1986 from bovine liver treated with insulin [4] when the analogous activity
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