Figure 5
The renal metabolomic profile of central carbon metabolites and amino acids associates with renal dysfunction in diabetes. White bars/ squares − Non-diabetic db/m mice (C); Black bars/dots diabetic db/db mice (D); Blue bars/triangles − diabetic db/db mice + 0.6 mg/kg/day MitoQ intragastrically (DMitoQ); Red bars/squares diabetic db/db mice + 3 mg/kg/day ramipril intragastrically (DRam); Grey bars/dots - diabetic db/db mice + combination of MitoQ and ramipril (DCoAd). n = 6 mice/group. (A) Bioinformatic scores plot of the OPLS-DA statistical bioinformatic model of all metabolomics data, which demonstrates clear separation among mouse groups along the predictive component axis (x axis), with intra-group variability along the orthogonal (y axis). (B) Table of the most influential metabolites which define the differences between diabetic (D) and all other mouse groups. b-f Renal cortical concentrations of (C) glycolytic/gluconeogenic intermediates glucose 6-phosphate (G6P, left), fructose 6-phosphate (F6P) and the TCA cycle intermediates citrate-isocitrate (right); (D) oxidised nicotinamide adenine dinucleotides NADP+ (left) and (NAD+, right); (E) the energy storage molecules creatinine phosphate (Cre-PO4, left), guanosine diphosphate (GDP, right) and (F) cytidine monophsophate (CMP, left); and the amino acid glycine (right). (G) Table of Pearson’s correlation coefficients for associations between renal function (GFR and 24 h urinary AER) and the renal cortical metabolites. CCM- central carbon metabolite; AAA- amino acid analyte. *P < 0.05 vs C by 1 W ANOVA/Tukey’s Post-hoc; † P < 0.05 vs D by 1 W ANOVA/Tukey’s Post-hoc; ‡ P < 0.05 vs D by Student’s unpaired t test.
