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L-serine dose-dependently ameliorates high-selenium-induced insulin resistance in mice
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DOI：10.1016/j.jnutbio.2026.110432.png)
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Abstract
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• Dietary L‑serine dose-dependently ameliorates insulin resistance (IR) and glucose intolerance induced by high selenium (0.8mg/kg) in C57BL/6 mice. • The functional threshold for L‑serine efficacy lies between 0.7% and 1.4% of dietary protein (≈96–182mg/kg/d), with broader molecular remodeling observed at ≥2.1%. • Direct LC-MS/MS quantification demonstrates a dose-dependent increase in the hepatic SAM/SAH methylation index, providing direct biochemical evidence that L‑serine replenishes the one-carbon pool consumed during selenium detoxification. • Recovery of PI3K-AKT-mTOR signaling and increased selenoprotein expression were observed across liver, muscle, and pancreas in a tissue-specific, dose-dependent manner. • NCT503 induces hyperhomocysteinaemia and lowers the hepatic SAM/SAH methylation index, supporting its role as a mechanistic comparator for distinguishing PHGDH inhibition from L‑serine substrate replenishment.
Keywords:
High selenium
Insulin resistance
L‑serine supplementation
One-carbon metabolism
SAM/SAH methylation index
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