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  • Anthraquinone-type inhibitor of α-glucosidase enhances glucose uptake by activating an insulin-like signaling pathway in C2C12 myotubes.

Anthraquinone-type inhibitor of α-glucosidase enhances glucose uptake by activating an insulin-like signaling pathway in C2C12 myotubes.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (2019-05-10)
Md Badrul Alam, Vivek K Bajpai, Jeong-Sic Ra, Ji-Young Lim, Hongyan An, Shruti Shukla, Khong Trong Quan, Imran Khan, Yun Suk Huh, Young-Kyu Han, MinKyun Na, Sang-Han Lee
ABSTRACT

This study assesses the ability of anthraquinone derivative, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone (MTAQ) to decrease postprandial hyperglycemia or enhance glucose uptake and to elucidate the underlying molecular mechanism. We investigated α-glucosidase inhibition, glucose uptake, and translocation of glucose transporter 4 (GLUT4) in C2C12 myotubes. The data indicate that MTAQ strongly inhibited α-glucosidase activity in a concentration-dependent manner, with an IC50 value of 6.49 ± 1.31 μM, and functioned as a reversible competitive inhibitor, with a dissociation constant of 41.88 μM. Moreover, MTAQ significantly augmented basal and insulin-stimulated glucose uptake as well as translocation of GLUT4 to the plasma membrane. It also stimulated the phosphorylation of insulin receptor β isoform, insulin receptor substrate-1,3-phosphoinositide-dependent protein kinase 1, and protein kinase B (AKT). A pretreatment with an AKT inhibitor, LY294002, attenuated the ability of MTAQ to activate an insulin-like signaling pathway and to enhance basal and insulin-stimulated glucose uptake and stimulate GLUT4 translocation to the plasma membrane. These findings reveal the fact that MTAQ may have potential for the development of new antidiabetic drugs to manage blood glucose levels.