Abstract
Herein, we determined whether α-Spinasterol, a stigmastane-type phytosterol isolated from Aster pseudoglehnii, potentially impacts glucose uptake and glucose-stimulated insulin secretion in skeletal muscle cells and pancreatic β-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. α-Spinasterol, isolated from the n-hexane fraction, enhanced glucose uptake with no toxic effects on C2C12 cells. Additionally, α-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, α-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). α-Spinasterol enhanced the expression of associated proteins, including insulin receptor substrate-2, peroxisome proliferator-activated receptor γ, and pancreatic and duodenal homeobox 1, as determined using Western blotting. The insulin secretory effect of α-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. α-Spinasterol isolated from A. pseudoglehnii may improve hyperglycemia by improving glucose uptake into skeletal muscle cells and enhancing insulin secretion in pancreatic β-cells. Accordingly, α-Spinasterol could be a potential candidate for anti-T2D therapy.
Highlights
Type 2 diabetes (T2D) is a steadily growing metabolic disease worldwide, characterized by a decline in insulin secretion from pancreatic β-cells and impaired insulin function in insulin-target tissues, such as skeletal muscle [1]
We determined whether α-Spinasterol, a stigmastane-type phytosterol isolated from A. pseudoglehnii, potentially impacts glucose uptake and glucose-stimulated insulin secretion in skeletal muscle cells and pancreatic β-cells, respectively
The chemical structure of the compound was identified as αSpinasterol by analysis of the MS and 1D nuclear magnetic resonance (NMR) data and by comparison with those reported in the literature [16]
Summary
Type 2 diabetes (T2D) is a steadily growing metabolic disease worldwide, characterized by a decline in insulin secretion from pancreatic β-cells and impaired insulin function in insulin-target tissues, such as skeletal muscle [1]. Skeletal muscle is a glucose-metabolic organ, where 70–80% of insulin-dependent glucose uptake reportedly occurs after glucose intake [2]. A previous study has revealed that limonene isolated from citrus fruits could induce glucose uptake via the Akt pathway in C2C12 skeletal muscle cells [3]. Eucalyptus, cumin, and mint has been shown to induce glucose uptake by upregulating Akt and glucose transporter type 4 (GLUT-4) in C2C12 cells [4,5]. Found in cereals, can reportedly induce glucose uptake by upregulating insulin receptor substrate-1 (IRS-1) and Akt [6]. Based on the above literature, Akt, GLUT-4, and IRS-1 play a central role in enhancing glucose uptake in skeletal muscle cells
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