Evidence mapPaperPMID 39789350Full record

ArticleBiological trace element research2025

Activation of the De Novo Serine Synthesis Pathway and Disruption of Insulin Signaling Induced by Supplemental SeMet in Vitro.

Shuo Zhan, Jiaqiang Huang, Yiqun Liu, Feng Han, Jianrong Wang, Qin Wang, Zhenwu Huang

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Article in Biological trace element research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Shuo ZhanDepartment of Nutrition and Metabolism, Chinese Center for Disease Control and Prevention, National Institute for Nutrition and Health, Beijing, 100050, China.
Jiaqiang HuangBeijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing, 100193, China.
Yiqun LiuDepartment of Nutrition and Metabolism, Chinese Center for Disease Control and Prevention, National Institute for Nutrition and Health, Beijing, 100050, China.
Feng HanDepartment of Nutrition and Metabolism, Chinese Center for Disease Control and Prevention, National Institute for Nutrition and Health, Beijing, 100050, China.
Jianrong WangDepartment of Nutrition and Metabolism, Chinese Center for Disease Control and Prevention, National Institute for Nutrition and Health, Beijing, 100050, China.
Qin WangDepartment of Nutrition and Metabolism, Chinese Center for Disease Control and Prevention, National Institute for Nutrition and Health, Beijing, 100050, China. wangqin@ninh.chinacdc.cn.
Zhenwu HuangDepartment of Nutrition and Metabolism, Chinese Center for Disease Control and Prevention, National Institute for Nutrition and Health, Beijing, 100050, China. huangzw@ninh.chinacdc.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Selenium (Se) intake or selenoprotein overexpression can cause abnormal glucose metabolism and increase the risk of type 2 diabetes (T2D). The purpose of this study is to observe whether glycolysis bypass in the de novo serine synthesis pathway (SSP) is activated under high-Se stress in vitro. Initially, HCT-116, L02, HepG2, and differentiated C2C12 cells were exposed to five selenomethionine (SeMet) concentrations (0.001 to 10 µmol/L) for 48 h. The expressions of glutathione peroxidase 1 (GPX1), selenoprotein P (SELENOP), 3-phosphoglycerate dehydrogenase (PHGDH), and serine hydroxy-methyltransferases 1 (SHMT1) were assessed by western blotting (WB). Then, corresponding to the peak expressions of GPX1, SELENOP, and PHGDH, 0.1 µmol/L SeMet was identified as the highest intervention concentration. With more detailed levels of SeMet (0.001 to 0.1 µmol/L) given, the differentiated C2C12 cells were treated for 48 h to analyze the expressions of selenoproteins, enzymes related with serine metabolism and insulin signaling pathway. Among the four cell lines, the expressions of selenoproteins and metabolic enzymes of serine in C2C12 cells were more sensitive to changes in Se concentrations, which was similar to that in L02 cells. In C2C12 cells, the expressions of GPX1, SELENOP, selenoprotein N (SELENON), PHGDH, and SHMT1 exhibited a parabolic inflection point at SeMet concentrations of 0.05 µmol/L or 0.075 µmol/L, while 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) showed no such trend. After 15 min of insulin stimulation, glucose retained more in the culture medium due to the decreased uptake by C2C12 cells. The expressions of key enzymes (AKT, AKT (Ser-473), AKT (Thr-308), mTOR, and PI3K) in the PI3K-AKT-mTOR signaling pathway decreased with the increased level of SeMet. This study demonstrated that excessive Se intake could induce abnormal glucose metabolism via SSP and impair the normal signaling of insulin in the differentiated C2C12 cells.

Indexed as

InsulinSelenomethionineSerineSignal TransductionAnimalsCell LineGlutathione Peroxidase GPX1Hep G2 CellsHumansMiceGlutathione Peroxidase GPX1InsulinSelenomethionineSerineC2C12 cellsPHGDHPI3K-AKT-mTORSelenoproteinsSeMet

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.