Polygonatum sibiricum polysaccharides (PSP) improve the palmitic acid (PA)-induced inhibition of survival, inflammation, and glucose uptake in skeletal muscle cells

ABSTRACT

Polygonatum sibiricum polysaccharides (PSP) can decrease the levels of fasting blood glucose, total cholesterol, and triglyceride (TG) in hyperlipidemic and diabetic animals. It can also reduce inflammatory cytokines and promote glucose uptake in adipocytes. However, the underlying molecular mechanisms of PSP in improving insulin resistance (IR) in skeletal muscle remain unclear. In this study, palmitic acid (PA) induced an IR model in L6 myotubes. After treatment, cell proliferation was measured using the CCK8. miR-340-3p, glucose transporter 4 (GLUT-4), and interleukin-1 receptor-associated kinase 3 (IRAK3) expression was measured by qRT-PCR. IRAK3 protein levels were measured by Western blotting. Glucose in the cell supernatant, TG concentration in L6 myotubes, and the levels of IL-1β, IL-6, and TNF-α were measured by an ELISA. We found that cell survival, glucose uptake, and GLUT-4 expression in L6 myotubes were significantly suppressed, while lipid accumulation and inflammatory factor levels were enhanced by PA stimulation. Furthermore, PSP treatment markedly alleviated these effects. Interestingly, PSP also significantly reduced the upregulated expression of miR-340-3p in the L6 myotube model of IR. Furthermore, overexpression of miR-340-3p reversed the beneficial effects of PSP in the same IR model. miR-340-3p can bind to the 3′-untranslated regions of IRAK3. Additionally, PA treatment inhibited IRAK3 expression, whereas PSP treatment enhanced IRAK3 expression in L6 myotubes. Additionally, miR-340-3p also inhibited IRAK3 expression in L6 myotubes. Taken together, PSP improved inflammation and glucose uptake in PA-treated L6 myotubes by regulating miR-340-3p/IRAK3, suggesting that PSP may be suitable as a novel therapeutic agent for IR.

KEYWORDS:

• Diabetes mellitus
• glucose intolerance
• microRNAs
• Polygonatum
• polysaccharides
• skeletal muscle

Availability of Data and Materials

All data during the study appear in the submitted article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Jia-luo Cai and Xiao-ping Li contributed to the conception and design of the work, acquisition of data, analysis and interpretation of data, and drafting of the manuscript. Yi-lin Zhu, Gang-qiang Yi, Wei Wang, and Xin-yu Chen contributed to the conception and design of the work and acquisition of data. Deng, Yang, and Cai made substantial contributions to data acquisition, analysis, and interpretation of data. Tong, Zhou, and Tian made substantial contributions to the acquisition of data. Xia and Liu made substantial contributions to conception and design and critically revised it for important intellectual content. All authors have approved this manuscript.

Supplementary material

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Additional information

Funding

The present study was supported by grants from the National Administration of Traditional Chinese Medicine of the People’s Republic of China Construction Project of Zhang Zhiguo Heritage Studio Related to the Old Chinese Medicine Experts (No. 2016), the Youth Program of the Natural Science Foundation of Hunan Province, China (the Youth Program of the Natural Science Foundation of Hunan province, China No. 2019JJ5041), the Health Special of Scientific Research Projects of Hunan Province, China (the Health Special of Scientific Research Projects of Hunan province, China No. B2019-06), Research Fund of the Hunan University of Chinese Medicine, China (Research Fund of the of Hunan University of Chinese Medicine, China No. 2020XJJJ045 and 2019XJJJ025), and Scientific Research Key Program of Hunan University of Chinese Medicine, China (No.2021016). The funding bodies had no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript, which are all the responsibilities of the authors.