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

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.

Glycolipids Derived from the Korean Endemic Plant Aruncus aethusifolius Inducing Glucose Uptake in Mouse Skeletal Muscle C2C12 Cells

“…In general, predicted molecular docking results and experimental results do not always agree well because a variety of factors can be involved, such as uptake, stability, and other interactions of the compounds, but in this study, the experimental results and molecular docking results agree well, suggesting the anti-diabetic potential of gingerglycolipid A. The evaluation of C2C12 cell glucose uptake and the involvement of various molecular factors, such as PPARγ, IRS-1, p-IRS-1, AMPK, and p-AMPK shed light on the intricate regulatory mechanisms that govern glucose homeostasis in skeletal muscle cells [20][21][22]. These factors play significant roles in glucose uptake and insulin sensitivity, and their interactions with, and effects on, metabolic health are significant.…”

Development of quality control parameters for two Bhutanese medicinal plants (Aster flaccidus Bunge and Aster diplostephioides (DC.) Benth. ex C.B.Clarke) using traditional and modern pharmacognostical platforms

“…Both α-spinasterol and syringaresinol also exhibited anti-diabetic properties mainly by inhibiting α-glucosidase enzyme activity [ 62 , 63 ]. Alpha-spinosterol also enhanced insulin secretion by pancreatic β-cells of the rat insulinoma INS-1 cells in response to high glucose concentration [ 64 ]. These compounds also exhibited other activities, including anti-tumour, anti-nociceptive, neuroprotective, and anti-aging properties ( Table 4 ).…”

Pharmacology of α‐spinasterol, a phytosterol with nutraceutical values: A review

“…α‐Spinasterol enhanced the expression of insulin receptor substrate‐2 (IRS‐2), and peroxisome proliferator‐activated receptor γ (PPARγ) in these cells. The authors conclude that α‐spinasterol may ameliorate hyperglycaemia by improving glucose uptake into skeletal muscle cells and enhancing insulin secretion from pancreatic β‐cells (Lee et al, 2022).…”

“…α-Spinasterol enhanced the expression of insulin receptor substrate-2 (IRS-2), and peroxisome proliferator-activated receptor γ (PPARγ) in these cells. The authors conclude that α-spinasterol may ameliorate hyperglycaemia by improving glucose uptake into skeletal muscle cells and enhancing insulin secretion from pancreatic β-cells(Lee et al, 2022).Recent molecular docking studies suggest that α-spinasterol acetate could inhibit PTP1B (protein tyrosine phosphatase 1 B), a negative regulator of insulin signalling. Inhibition of this enzyme results in increased insulin signalling(Hsing, Rathnasamy, Dianita, & Wahab, 2020).Antioxidant and antiinflammatory potential of α-spinasterol may help in the regeneration of insulin secreting β-cells.…”