[Effects of serine and NCT503 on improving abnormal glucose metabolism in C2C12 cells cultured in a high selenium medium].

Objective: To evaluate the effects of serine supplementation and the 3-phosphoglycerate dehydrogenase(PHGDH)inhibitor NCT503 on the remodeling of glucose metabolism in C2C12 cells under high-selenium(Se) conditions.

Methods: C2C12 cells were divided into four groups: control group, high-selenium control group, serine intervention group, and NCT503 intervention group. After 48 hours of treatment, all cells were stimulated with insulin for 15 minutes. The glucose concentration in the cell culture medium was measured before and after insulin stimulation. The expression levels of selenoproteins: glutathione peroxidase 1 and selenoprotein N, serine synthesis and metabolism enzymes: PHGDH, hydroxy-methyltransferases 1(SHMT1), 5, 10-methylenetetrahydrofolate reductase(MTHFR), methionine synthase(MS), and signaling factors: mammalian target of rapamycin, protein kinase B(AKT), Akt1 kinase phosphorylated on Ser 473, Akt1 kinase phosphorylated on Thr 308, and phosphatidylinositol 3 kinase were assessed by Western blotting.

Results: Compared with the high-selenium control group, both the serine and NCT503 intervention groups improved insulin sensitivity in C2C12 cells, as indicated by an increased glucose difference in the culture medium before and after insulin stimulation(P<0.05). In the serine intervention group, the expression of serine synthesis enzyme PHGDH and metabolic enzymes SHMT1 and MS was reduced compared to the high-selenium control group(P<0.05). In the NCT503 intervention group, only the expression of some serine metabolic enzymes(SHMT1 and MS) was decreased compared to the high-selenium control group(P<0.05).

Conclusion: Both exogenous serine and the PHGDH inhibitor NCT503 can alleviate high-selenium-induced abnormalities in glucose metabolism in C2C12 cells. However, serine, being a natural component of the human body, can also feedback inhibit the key enzyme PHGDH in serine synthesis.