D-Serine activates glycolysis via mTOR pathway in kidney remodeling and suppresses onset of diabetes

D-Serine, a long-term undetected enantiomer of serine1,2, is a novel biomarker that reflects kidney function and disease activity3-5 and has unclear physiological functions. Here we show that D-serine is a physiological molecule that promotes tissue remodeling and suppresses the onset of diabetes. D-serine is quickly and dominantly distributed to the kidney upon injection in mice, suggesting that the kidney is a key target organ. Unilateral nephrectomy in human living kidney donors decreases urinary excretion and thus increases the blood level of D-serine, which in turn promotes the compensatory enlargement of the remnant kidney in mouse model. D-Serine activates cell cycle for tissue remodeling through an mTOR-related pathway, which promotes metabolic reprograming to glycolytic activation. In rodent diabetic model, D-serine promotes glycolysis in the kidney and suppresses the surge of blood glucose levels. D-Serine has physiological activity that influences kidney function and maintains metabolic homeostasis to reduce diabetic propensity. Overall design: We compared transcriptome of D-serine-treated mice and vehicle-treated mice in triplicates.