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

Jessica Gooding; Lei Cao; Courtney Whitaker; Jean-Marie Mwiza; Mizpha Fernander; Faihaa Ahmed; Zach Acuff; Susan McRitchie; Susan Sumner; Elimelda Moige Ongeri

doi:10.1186/s12882-019-1313-2

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 acid^a	Increase in WT	Bile acids (lipid metabolism)
Ergothioneine^a	Increase in WT	Gut/dietary source (histidine metabolism)
Tyrosyl-Valine^a	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-glucuronide^a	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 acid^a	Increase at 4 and 8 weeks	Amino acid metabolism (phenylalanine polyphenol metabolism; uremia)
Indole-3-carboxilic acid-O-sulphate^a	Increase	Indole metabolism
Fenoprofen glucuronide^a	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)

^aVIP ≤ 2 but consistent significant increases at both 4 and 8 weeks post STZ

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