Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (11): 38-47.doi: 10.6040/j.issn.1671-7554.0.2023.0753

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Effects of NR4A1 on thapsigargin-induced glucose metabolism dysfunction in C2C12 myotube cells

LU Xingchen1, QIANG Ye2, LIU Xinyu3, ZUO Dan4, JIANG Zihan1, ZHANG Yuchao4, LIU Yuantao5, MA Xiaoli2   

  1. 1. Qingdao Clinical Medical School of Qingdao University, Qingdao Municipal Hospital, Qingdao 266011, Shandong, China;
    2. Endocrine Center, Qingdao Hospital of Rehabilitation University(Qingdao Municipal Hospital), Qingdao 266011, Shandong, China;
    3. Department of Clinical Nutrition, Yantai Yuhuangding Hospital, Laishan Branch, Yantai 264000, Shandong, China;
    4. Editorial Office of Medical Journal, Qingdao Hospital of Rehabilitation University(Qingdao Municipal Hospital), Qingdao 266011, Shandong, China;
    5. Department of Endocrinology, Qilu Hospital of Shandong University(Qingdao), Qingdao 266011, Shandong, China
  • Published:2023-12-12

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Abstract: Objective To explore the effects and mechanism of NR4A1 on thapsigargin(TG)-induced glucose metabolism dysfunction in C2C12 myotube cells. Methods C2C12 cells were induced to differentiate into mature myotube cells in vitro. Cells stimulated with 20 nmol/L insulin for 10 minutes were labeled as insulin group, while cells without special treatment were labeled as control group. The phosphatidyl inositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway and protein expression of NR4A1 were determined with Western blotting. The viability of C2C12 myotube cells treated with TG concentration gradient was detected with CCK8. After a glucose metabolism impaired cell model was established, the cells were divided into control group, ethanol(EtOH)group, and TG group. After treatment, insulin was added, then glucose consumption level was measured with a glucose assay kit. The protein expressions of NR4A1, p-PI3K and p-AKT were detected with Western blotting. After the cells were infected with lentivirus and screened, those with stable overexpression of NR4A1 were obtained and subjected to TG treatment. After that, the cells were divided into Ad-NC group, Ad-NC+TG group, and Ad-NR4A1+TG group. After differentiation and maturation, insulin was added to detect the glucose consumption level and the expressions of NR4A1, p-PI3K and p-AKT. Results Compared with the control group, the insulin group showed significantly higher phosphorylation of the PI3K/AKT pathway and NR4A1 expression(P<0.01). CCK-8 results showed that the cell viability significantly decreased after 1 μmol/L of TG treatment(P<0.01). Compared with the EtOH group, the TG group showed decreased glucose consumption, reduced NR4A1 expression, and inhibited PI3K/AKT phosphorylation(P<0.01). Compared with the Ad-NC+TG group, the Ad-NR4A1+TG group showed an increase in glucose consumption with insulin stimulation(P<0.05), and significant activation of PI3K/KT signaling pathway(P<0.05). Conclusion TG induces glucose metabolism dysfunction in C2C12 myotube cells, while NR4A1 can improve such dysfunction, which may be mediated through the PI3K/AKT signaling pathway.

Key words: NR4A1, C2C12 myotube cells, Phosphatidyl inositol-3-kinase/protein kinase B signaling pathway, Thapsigargin, Glucose metabolism

CLC Number: 

  • R574
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