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Int J Biol Sci 2023; 19(5):1579-1596. doi:10.7150/ijbs.80125 This issue Cite

Research Paper

Tectorigenin targets PKACα to promote GLUT4 expression in skeletal muscle and improve insulin resistance in vitro and in vivo

Xinlei Yao1,2,3, Lei Liu1, Wenjun Shao1, Miao Bai1, Xiaohan Ding1, Geng Wang1, Shuyue Wang1,3, Lihua Zheng1,3, Ying Sun1,3, Guannan Wang1,3, Yanxin Huang1,3, Chunlei Yu1,3, Zhenbo Song1,3, Yongli Bao1,3, Shaonian Yang4, Luguo Sun1,3✉

1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
2. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
3. Research Center of Agriculture and Medicine gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China.
4. The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, Stockholm, Sweden.

✉ Corresponding author: Email: sunlg388edu.cn (Luguo Sun). Tel: 86-0431-8916-5922; Fax: 86-0431-8916-5917.

Citation:
Yao X, Liu L, Shao W, Bai M, Ding X, Wang G, Wang S, Zheng L, Sun Y, Wang G, Huang Y, Yu C, Song Z, Bao Y, Yang S, Sun L. Tectorigenin targets PKACα to promote GLUT4 expression in skeletal muscle and improve insulin resistance in vitro and in vivo. Int J Biol Sci 2023; 19(5):1579-1596. doi:10.7150/ijbs.80125. https://www.ijbs.com/v19p1579.htm
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Abstract

Graphic abstract

The decreased expression and dysfunction of glucose transporter 4 (GLUT4), the insulin-responsive glucose transporter, are closely related to the occurrence of insulin resistance (IR). To improve the expression of GLUT4 may represent a promising strategy to prevent and treat IR and type 2 diabetes (T2DM). Here, we demonstrate that the natural compound tectorigenin (TG) enhances GLUT4 expression, glucose uptake and insulin responsiveness via activating AMP-activated protein kinase (AMPK)/myocyte enhancer factor 2 (MEF2) signaling in both normal and IR skeletal muscle cells and tissues. Accordingly, prophylactic and therapeutic uses of TG can significantly ameliorate IR and hyperglycemia in T2DM mice. Mechanistically, we identify protein kinase A catalytic subunit α (PKACα) as the target of TG to increase GLUT4 expression and TG-PKACα binding promotes the dissociation of PKACα from the regulatory subunits, leading to the activation of PKA/AMPK signaling. PKACα knockdown in local quadriceps muscles almost completely abolished the therapeutic effects of TG on IR and T2DM, as well as the enhancement on AMPK signaling and GLUT4 expression in skeletal muscle. This study supports TG as a new drug candidate to treat IR and its related diseases, but also enriches our knowledge of PKA signaling in glucose metabolism in skeletal muscle.

Keywords: tectorigenin, insulin resistance, GLUT4, AMPK, PKACα

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APA
Yao, X., Liu, L., Shao, W., Bai, M., Ding, X., Wang, G., Wang, S., Zheng, L., Sun, Y., Wang, G., Huang, Y., Yu, C., Song, Z., Bao, Y., Yang, S., Sun, L. (2023). Tectorigenin targets PKACα to promote GLUT4 expression in skeletal muscle and improve insulin resistance in vitro and in vivo. International Journal of Biological Sciences, 19(5), 1579-1596. https://doi.org/10.7150/ijbs.80125.

ACS
Yao, X.; Liu, L.; Shao, W.; Bai, M.; Ding, X.; Wang, G.; Wang, S.; Zheng, L.; Sun, Y.; Wang, G.; Huang, Y.; Yu, C.; Song, Z.; Bao, Y.; Yang, S.; Sun, L. Tectorigenin targets PKACα to promote GLUT4 expression in skeletal muscle and improve insulin resistance in vitro and in vivo. Int. J. Biol. Sci. 2023, 19 (5), 1579-1596. DOI: 10.7150/ijbs.80125.

NLM
Yao X, Liu L, Shao W, Bai M, Ding X, Wang G, Wang S, Zheng L, Sun Y, Wang G, Huang Y, Yu C, Song Z, Bao Y, Yang S, Sun L. Tectorigenin targets PKACα to promote GLUT4 expression in skeletal muscle and improve insulin resistance in vitro and in vivo. Int J Biol Sci 2023; 19(5):1579-1596. doi:10.7150/ijbs.80125. https://www.ijbs.com/v19p1579.htm

CSE
Yao X, Liu L, Shao W, Bai M, Ding X, Wang G, Wang S, Zheng L, Sun Y, Wang G, Huang Y, Yu C, Song Z, Bao Y, Yang S, Sun L. 2023. Tectorigenin targets PKACα to promote GLUT4 expression in skeletal muscle and improve insulin resistance in vitro and in vivo. Int J Biol Sci. 19(5):1579-1596.

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