Fig 2: Dietary methionine restriction restores connectivity between folate and methionine cycles and increases one-carbon donor availability. (A) A schematic representation of select metabolites and reactions related to one-carbon metabolism. The blue dash line indicates loss of glycine N-methyltransferase (GNMT). Italicized metabolites (Hcy, homocysteine; N-formylmethionine; THF, tetrahydrofolate) were not measured. (B) Liver 5-methyltetrahydrofolate (5-MeTHF) and (C) total adenine nucleotides (nmol/g; n = 7–8 per group). (D) Liver methylenetetrahydrofolate reductase (MTHFR) as determined by immunoblotting with a representative immunoblot in GNMT knockout (KO) and wild-type (WT) littermates on a control (CON) and methionine-restricted (MR) diet (arbitrary units; n = 6–8 per group). (E) Representative image of phospho-MTHFR and unphosphorylated MTHFR as determined by immunoblotting. (F) Liver phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1) as determined by immunoblotting with a representative immunoblot (arbitrary units; n = 7–8 per group). (G) Liver serine and (H) glycine (nmol/g; n = 7–8 per group). (I) Liver choline, (J) betaine, (K) dimethylglycine, and (L) sarcosine (nmol/g; n = 6–8 per group). Data are presented as mean ± SEM. ND = not detected. ∗p < 0.05. ∗∗p < 0.01. ∗∗∗p < 0.001. ∗∗∗∗p < 0.0001.

Fig 3: SCU can down-regulate Hcy levels in type 2 diabetic rats. (A) The levels of serum Hcy. (B) Western blot detection of CSE, CBS, MTHFR and MTR. (C) Immunohistochemistry results of CSE, CBS, MTHFR and MTR. A. normal group; B. model group; C. SCU low dose treatment group; D. SCU high dose treatment group; E. Rosiglitazone treatment group. (D) The level of Serum VitB6, VitB12 and folic acid. #Represents the statistically significant difference from the normal group (p < 0.05), *Represents the statistically significant difference from the model group (p < 0.05).