Abstract
To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analyzed its oral pharmacokinetics and its effects on (a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), (b) insulin signaling in the liver and (c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associated with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation, while sustaining glycaemia through the liver-based mechanisms of glycolysis control.
Highlights
Insulin resistance refers to a poor response of insulin receptors through the phosphatidylinositol-3-kinase (PI3K) pathway [1]
We focused on hepatic glycogenesis and gluconeogenesis pathways, as well as on the secretion profile of several hormones and mediators involved in the control of the insulin-glucose metabolic homeostasis axis: leptin, adiponectin, or ghrelin [1,20,21,22]
Natural inositols, as insulinomimetics, have gained attention as potential functional foods that might help to prevent the development of insulin resistance and diabetes type 2
Summary
Insulin resistance refers to a poor response of insulin receptors through the phosphatidylinositol-3-kinase (PI3K) pathway [1]. This state demands a greater secretion of insulin by the pancreas, but without effective control on blood glucose levels. Insulin resistance is associated with high sugar or fat diets, Nutrients 2020, 12, 2030; doi:10.3390/nu12072030 www.mdpi.com/journal/nutrients. Nutrients 2020, 12, 2030 obesity, hyperglycemia and hyperinsulinemia. This is the prelude to type 2 diabetes mellitus (T2DM), a condition in which cells cannot respond properly to insulin [1]. Alterations in inositol metabolism are evident in situations of insulin-resistance leading to T2DM
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