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Table 8 Summary of metabolic pathways for metabolites with significant changes in levels that associate with meprin β expression or deficiency and STZ-induced type 1 diabetes

From: Meprin β metalloproteases associated with differential metabolite profiles in the plasma and urine of mice with type 1 diabetes and diabetic nephropathy

Metabolite Increase/decrease Pathways
Group 1: changed levels in plasma associate with meprin expression or deficiency
 Taurocholic acid Increases in WT Bile acids/lipid metabolism
 LysoPC(16:1(9Z)) Decreases in WT Lipid metabolism
 Indoxyl sulfate Increases in WT oxidative stress
Group 2: 8 changes in urine associate with meprin β expression or deficiency
 Taurocholic acida Increase in WT Bile acids (lipid metabolism)
 Ergothioneinea Increase in WT Gut/dietary source (histidine metabolism)
 Tyrosyl-Valinea Increase in WT Protein degradation (aromatic amino acid metabolism)
 Prenyl glucoside Decrease in WT Gut/dietary (fatty acyl glucoside)
 Homovanillic acid sulfate increase in WT Catecholamine metabolism
 Cortisol Increase in WT Steroid hormone synthesis/stress response
 Aromadendrin 3,7-diglucoside Increase in WT Gut/dietary (flavonoid)
 Phloretin 2′-O-glucuronidea Increase in WT Gut/dietary (flavonoid)
 3,5-Dihydroxy-3′,4′-dimethoxy-6,7- methylenedioxyflavone 3-glucuronide Decrease in βKO Gut/dietary
 Pantothenic acid Decrease in βKO Gut/dietary
 Indoxyl glucuronide Decrease in βKO Indole metabolism/gut microbiota
Group 3: changed levels in plasma associate with STZ-induced type 1 diabetes but independent of meprin β expression
 Hippuric acida Increase at 4 and 8 weeks Amino acid metabolism (phenylalanine polyphenol metabolism; uremia)
 Indole-3-carboxilic acid-O-sulphatea Increase Indole metabolism
 Fenoprofen glucuronidea Increase NSAID metabolite
Group 4: Changed levels in urine associate with STZ-induced type 1 diabetes but independent of meprin β expression
 Glycerophosphocholine Decrease Lipid metabolism (choline metabolism; glycerophosphocholine)
 Nicotinic acid Decrease Co-factor and vitamin (nicotinate and nicotinamide metabolism)
 1-Pyrroline-4-hydroxy-2-carboxylate Decrease Amino acid metabolism (arginine and proline metabolism)
 Indole-3-carboxylic acid Decrease Gut/Dietary (indole metabolism)
 a-L-threo-4-Hex-4-enopyranuronosyl-D-galacturonic acid Decrease Carbohydrate metabolism (glucuronic acid derivative)
  1. aVIP ≤ 2 but consistent significant increases at both 4 and 8 weeks post STZ