Dual Beneficial Effects of alpha-Spinasterol Isolated from Aster pseudoglehnii on Glucose Uptake in Skeletal Muscle Cells and Glucose-Stimulated Insulin Secretion in Pancreatic beta-Cells

Abstract

Herein, we determined whether alpha-Spinasterol, a stigmastane-type phytosterol isolated from Aster pseudoglehnii, potentially impacts glucose uptake and glucose-stimulated insulin secretion in skeletal muscle cells and pancreatic beta-cells, respectively. We observed that A. pseudoglehnii and its fractions enhanced glucose uptake, with no toxic effects on C2C12 cells, with the n-hexane fraction exhibiting the most potent effect. alpha-Spinasterol, isolated from the n-hexane fraction, enhanced glucose uptake with no toxic effects on C2C12 cells. Additionally, alpha-Spinasterol increased the expression of associated proteins, including insulin receptor substrate-1, AMP-activated protein kinase, and glucose transporter type 4, as determined by Western blotting. Furthermore, alpha-Spinasterol enhanced insulin secretion in response to high glucose concentrations, with no toxic effects on INS-1 cells; this effect was superior to that demonstrated by gliclazide (positive control), commonly prescribed to treat type 2 diabetes (T2D). alpha-Spinasterol enhanced the expression of associated proteins, including insulin receptor substrate-2, peroxisome proliferator-activated receptor gamma, and pancreatic and duodenal homeobox 1, as determined using Western blotting. The insulin secretory effect of alpha-Spinasterol was enhanced by a K+ channel blocker and L-type Ca2+ channel agonist and was suppressed by a K+ channel activator and L-type Ca2+ channel blocker. alpha-Spinasterol isolated from A. pseudoglehnii may improve hyperglycemia by improving glucose uptake into skeletal muscle cells and enhancing insulin secretion in pancreatic beta-cells. Accordingly, alpha-Spinasterol could be a potential candidate for anti-T2D therapy.