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Table 2 Metabolites shown as statistically significant (P < 0.05) when comparing non-diabetic/untreated and streptozotocin-induced diabetic/untreated rats in both independent studies

From: Metabolomic analysis of rat serum in streptozotocin-induced diabetes and after treatment with oral triethylenetetramine (TETA)

  Discovery Validation
Metabolite P-value Ratio (diabetic/non-diabetic) P-value Ratio (diabetic/non-diabetic)
Amino acids and related metabolites     
   Isovalerylalanine AND/OR isovalerylsarcosine 0.00049 8.20 0.00016 2.85
   5-Methoxytryptophan 0.00113 7.74 0.00038 2.13
   N-[O-Phosphono-pyridoxyl]-isoleucine 0.00150 2.46 0.00115 3.30
   Isoleucine AND/OR leucine AND/OR norleucine AND/OR N-methylvaline 0.00035 2.39 0.00067 1.51
   Arginine 0.02434 0.67 0.00016 0.54
   Beta-cyclohexyl-alanine 0.00411 0.66 0.00320 0.81
   Proline 0.00708 0.65 0.00320 0.77
   2-Methylserine AND/OR homoserine AND/OR allothreonine 0.00932 0.51 0.00024 0.41
   Oxoproline 0.03347 0.45 0.00038 0.50
   Tryptophan 0.00035 0.42 0.00016 0.44
Bile acids     
   24-Nor-5beta-cholane-3alpha,7alpha,12alpha,22,23-pentol 0.00127 2.84 0.00016 2.10
   24-Nor-5beta-chol-22-ene-3alpha,7alpha,12alpha-triol AND/OR (22R)-3alpha,7alpha,22-Trihydroxy-5beta-cholan-24-oic acid 0.02092 2.14 0.04937 1.71
   (22E)-3alpha,6beta,7beta-trihydroxy-5beta-chol-22-en-24-oic acid AND/OR 3,7-dihydroxy-12-oxocholanoic acid 0.03877 1.94 0.03376 3.09
   (22R)-3alpha,7alpha,22-trihydroxy-5beta-cholan-24-oic acid 0.03051 1.66 0.02334 1.92
   (22E)-12alpha-hydroxy-3-oxochola-1,4,22-trien-24-oic acid AND/OR 12alpha-hydroxy-3-oxochola-1,4,6-trien-24-oic acid 0.00067 0.85 0.00150 0.88
Dipeptides     
   Gamma-glutamyl-L-isoleucine AND/OR gamma-glutamyl-L-leucine 0.00035 3.79 0.00016 1.79
   (5-L-Glutamyl)-L-glutamine 0.00035 0.36 0.00016 0.58
Fatty acids and related metabolites     
   Methyl-hexadecanedioic acid AND/OR heptadecanedioic acid AND/OR 9,10-dihydroxy-13-hydroperoxy-11-octadecenoic acid 0.00172 3.41 0.00088 2.05
   Dodecenedioic acid AND/OR 9,12-dioxo-dodecanoic acid 0.00093 2.26 0.00067 1.50
   Octadecatrienoic acid 0.00708 1.90 0.00250 2.50
   Hydroperoxyoctadecadienoic acid 0.02434 1.46 0.01261 1.96
   Heptadecenoic acid 0.04694 1.26 0.03429 1.69
   Hexadecenoic acid AND/OR methyl-pentadecenoic acid AND/OR dimethyl-tetradecenoic acid 0.02434 0.63 0.00407 0.22
   Hydroxydecadienedienoic acid 0.04600 0.56 0.04125 0.75
   Hydroxydecanoic acid 0.00150 0.49 0.00051 0.46
Lysophospholipids     
   LysoPE(18:0) 0.03051 1.38 0.04937 1.20
   LysoPE(18:2) 0.00708 1.33 0.00016 2.44
   LysoPC(18:2) 0.03798 1.17 0.00029 1.26
   LysoPC(18:1) 0.01185 0.70 0.02014 0.67
   LysoPC(20:4) 0.01255 0.70 0.00021 0.60
   LysoPC(16:1) 0.02434 0.65 0.00051 0.21
   LysoPC(14:0) 0.00093 0.57 0.00250 0.29
   LysoPC(20:1) 0.00541 0.48 0.01261 0.61
   LysoPC(22:6) 0.00172 0.46 0.00320 0.46
   LysoPC(dm16:0) 0.00035 0.43 0.00088 0.56
   LysoPC(O-16:2) 0.02092 0.32 0.01255 0.22
   LysoPC(22:5) 0.00146 0.30 0.00021 0.27
Nucleosides, purine and pyrimidine metabolites     
   1,7-Dimethylxanthine AND/OR theobromine AND/OR theophylline 0.00035 3.40 0.00016 2.87
   Thionicotinamide-adenine-dinucleotide 0.00035 2.68 0.00021 1.64
   5-Methyl-2'-deoxycytidine 0.01255 2.54 0.00016 2.10
   Hydroxyadenine AND/OR guanine 0.00049 0.81 0.00021 0.77
   Cytosine 0.00049 0.73 0.00021 0.59
   Deoxycytidine 0.03389 0.48 0.00016 0.32
Phospholipids     
   PC(36:2) 0.00035 2.95 0.00016 1.76
   PE-NMe2(32:0) AND/OR PC(34:1) 0.00049 2.45 0.00115 1.23
   PE(36:2) 0.00172 2.28 0.00016 2.47
   PE(38:3) 0.00035 2.05 0.00051 1.44
   PC(2:0/O-18:0) AND/OR PC(O-16:0/4:0) 0.00310 1.95 0.00250 1.42
   PC(34:2) 0.00172 1.91 0.00016 1.38
   PC(36:2) 0.00172 1.88 0.00016 1.51
   PC(20:2/dm18:1) AND/OR PC(20:3/dm18:0) AND/OR PC(O-16:0/22:4) AND/OR PC(O-18:0/20:4) 0.04550 1.72 0.00082 1.37
   PE(38:2) 0.00067 1.59 0.00016 2.26
   PC(34:3) 0.00232 1.54 0.00024 2.30
   PC(36:4) 0.01185 1.52 0.00194 1.18
   PC(6:0/O-16:0) AND/OR PC(O-12:0/10:0) AND/OR PC(O-18:0/4:0) AND/OR PC(O-20:0/2:0) 0.00328 1.52 0.00220 1.62
   PC(40:5) 0.00172 1.49 0.00194 1.13
   PC(38:5) 0.00932 1.42 0.02837 1.06
   PC(40:8) 0.03389 1.26 0.00465 1.31
   PC(18:2/dm18:1) AND/OR PC(18:3/dm18:0) AND/OR PC(20:3/dm16:0) AND/OR PC(O-16:0/20:4) 0.04236 1.19 0.01789 1.15
   PC(32:1) 0.04694 0.84 0.00016 0.17
   PC(36:0) 0.00708 0.70 0.02837 0.90
   PC(16:0/O-16:0) AND/OR PC(O-14:0/18:0) 0.02689 0.69 0.00021 0.60
   PC(O-8:0/O-8:0) 0.00093 0.62 0.00150 0.63
   PC(44:9) 0.03347 0.61 0.00024 0.60
   PC(42:7) 0.03389 0.55 0.00016 0.71
   PC(18:1/dm18:1) AND/OR PC(18:2/dm18:0) AND/OR PC(20:2/dm16:0) AND/OR PC(O-16:0/20:3) AND/OR PC(20:4/dm18:1) 0.00415 0.53 0.00194 0.63
   PC(18:0/O-16:0) AND/OR PC(O-18:0/16:0) AND/OR PC(38:4) 0.01928 0.53 0.04937 0.86
   PC(34:4) 0.00218 0.47 0.00024 0.31
   PC(38:2) 0.00172 0.43 0.00051 0.60
   PC(18:0/dm18:1) AND/OR PC(18:1/dm18:0) AND/OR PC(18:2/O-18:0) AND/OR PC(20:1/dm16:0) AND/OR PC(P-18:0/18:1) AND/OR PC(20:3/dm18:1) 0.00232 0.32 0.00407 0.76
Short chain fatty acids and organic acids     
   Azelaic acid 0.00232 5.22 0.00051 1.68
   Oxopentanoic acid AND/OR methyl-oxobutanoic acid 0.00035 4.95 0.00088 1.78
   Hydroxybutanoic acid AND/OR methyl-hydroxybutanoic acid 0.01255 4.64 0.00016 3.13
   2-Ethylhydracrylic acid AND/OR hydroxy-methylbutyric acid 0.00035 4.18 0.00016 2.42
   Methylacetoacetic acid 0.00035 4.14 0.00150 1.40
   3-Butenoic acid 0.00035 3.79 0.00016 2.66
   2-Methylglutaconic acid AND/OR 2,3-dimethylmaleic acid AND/OR 2-methyleneglutaric acid AND/OR 3-hexenedioic acid 0.00035 3.61 0.00194 1.49
   Hydroxyacetone AND/OR propanoic acid AND/OR dihydroxybutyric acid AND/OR 4-deoxyerythronic acid 0.00086 2.66 0.00016 1.51
   Hydroxyhexanoic acid AND/OR 2-ethyl-2-hydroxybutyric acid 0.00093 2.51 0.00016 2.13
   Glyceric acid 0.01417 2.01 0.00024 3.33
   Isonicotinic acid AND/OR nicotinic acid AND/OR picolinic acid 0.01185 0.69 0.00650 0.86
   Hydroxybenzoic acid AND/OR salicylic acid 0.02689 0.57 0.04125 0.74
   Indolepyruvic acid 0.00150 0.56 0.00061 0.55
   Methylindolepyruvic acid 0.03347 0.49 0.00220 0.51
   Lactic acid 0.00415 0.34 0.00016 0.56
Sphingomyelines     
   SM(d18:1/18:1) 0.00541 1.73 0.00138 1.42
   SM(d18:1/22:1) 0.00919 0.75 0.00815 0.67
   SM(d18:1/14:0) 0.01517 0.60 0.00128 0.28
   SM(d18:1/22:0) 0.00049 0.53 0.00021 0.47
Vitamin D metabolites     
   1Alpha,25-dihydroxy-19-nor-22-oxavitamin D3 AND/OR 26,27-dinor-3alpha,6alpha,12alpha-trihydroxy-5beta-cholestan-24-one AND/OR linoleyl carnitine 0.00035 2.65 0.00038 3.36
   11Alpha-hemiglutaryloxy-1,25-dihydroxyvitamin D3 0.02086 1.39 0.03429 1.30
   (22E)-(24R)-1Alpha,24,25-trihydroxy-22,23-didehydrovitamin D3 0.01517 0.44 0.00021 0.29
Other metabolites     
   2,5,7,8-Tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman -glucuronide 0.03671 6.60 0.01123 5.60
   C12 SUGAR 0.00035 5.59 0.00016 5.52
   Harman 0.00035 5.00 0.00016 3.77
   1-O-Coumaroyl-beta-D-glucose AND/OR 4-O-beta-D-glucosyl-4-hydroxycinnamate AND/OR cis-beta-D-glucosyl-2-hydroxycinnamate AND/OR coumarinic acid-beta-D-glucoside AND/OR trans-beta-D-glucosyl-2-hydroxycinnamic acid 0.00035 3.97 0.00029 3.36
   Pteridine 0.00053 3.75 0.00051 2.28
   1-(4'-Hydroxyphenyl)ethanol AND/OR 3-methoxybenzyl alcohol AND/OR 4-hydroxyphenylethanol 0.00124 3.59 0.00016 1.86
   C6 SUGAR 0.00035 3.36 0.00016 3.35
   N-Formylpiperidine AND/OR 2-methylbutyrylglycine AND/OR 3-dehydrocarnitine 0.00127 3.09 0.00016 1.88
   Leucine phosphonic acid AND/OR norleucine phosphonate AND/OR N-trimethyl-2-aminoethylphosphonate 0.00146 2.72 0.00341 1.96
   2-Amino-2-methylbutanoate AND/OR amino-pentanoic acid AND/OR 4-methylaminobutyrate AND/OR betaine AND/OR isovaline AND/OR norvaline 0.00035 2.64 0.00029 1.60
   Sebacic acid AND/OR 1,8-diaminooctane AND/OR 2-amyl 3-butenoic acid AND/OR nonenoic acid AND/OR 4-hydroxynonenal AND/OR 6-methyl-5-octenoic acid 0.00919 2.51 0.00407 1.63
   4-Hydroxyphenylacetylglutamic acid 0.00035 2.50 0.00016 3.35
   Riboflavin 0.01742 2.21 0.00629 3.51
   Neuromedin B (1-3) 0.00049 2.10 0.00088 1.95
   12-Hydroxyjasmonic acid 12-O-beta-D-glucoside 0.04123 2.01 0.00239 5.74
   N-(2-hydroxy-2S-methyl-ethyl)-16,16-dimethyl-5Z,8Z,11Z,14Z-docosatetraenoyl amine AND/OR N-(2-methoxy-ethyl)-16,16-dimethyl-5Z,8Z,11Z,14Z-docosatetraenoyl amine 0.00179 1.80 0.00114 1.63
   4-Hydroxyphenylacetonitrile AND/OR hydroxyindole AND/OR 2,5,6-trihydroxy-5,6-dihydroquinoline AND/OR 3-succinoylpyridine AND/OR adrenochrome AND/OR hippuric acid 0.00067 1.80 0.00320 1.48
   4-Hydroxy-2-quinolinecarboxylic acid AND/OR indole-3-glyoxylic acid AND/OR kynurenic acid 0.00937 1.78 0.01789 1.54
   2,6-Dimethoxyphenol AND/OR 4-hydroxy-3-methoxy-benzenemethanol AND/OR hydroxytyrosol 0.00950 1.69 0.03389 2.44
   Urea 0.00067 1.68 0.00115 1.44
   Dolichyl phosphate AND/OR 1,25-dihydroxy-2-nor-1,2-secovitamin D3 AND/OR 1alpha,25-dihydroxy-19-norvitamin D3 0.04486 1.66 0.04331 1.82
   2,5,6-Trihydroxy-5,6-dihydroquinoline AND/OR 3-succinoylpyridine AND/OR adrenochrome AND/OR hippurate 0.03051 1.64 0.00194 1.55
   Bacteriohopane-32,33,34,35-tetrol 0.03075 1.59 0.00705 1.92
   Acetylcarnitine 0.02789 1.56 0.00038 1.90
   Palmitoyl glucuronide 0.02689 1.56 0.00016 1.49
   2-Phenylethanol glucuronide 0.01928 1.46 0.00051 1.88
   Methylnitrosourea 0.00127 1.45 0.00038 1.98
   DG(36:4) 0.02689 1.34 0.00115 2.65
   1-(9Z,1Z-octadecadienoyl)-2-(10Z,13Z,16Z,19Z-docosatetraenoyl)-3-O-[hydroxymethyl-N,N,N-trimethyl-beta-alanine]-glycerol 0.00310 1.30 0.00016 1.09
   (22alpha)-Hydroxy-cholestanol AND/OR 3alpha,7alpha-dihydroxy-5beta-cholestane AND/OR 5beta-cholestane-3alpha,12alpha-diol 0.03051 1.28 0.01261 1.33
   3-Amino-3-(4-hydroxyphenyl)propanoic acid AND/OR 3-hydroxyphenylalanine AND/OR threo-phenylserine AND/OR tyrosine 0.04694 0.84 0.00021 0.66
   5-Hydroxy-2-polyprenylphenol AND/OR geranylhydroquinone 0.00919 0.80 0.00937 0.71
   Glycinamide AND/OR N-acetyldiamine AND/OR N-methylurea AND/OR N-nitrosodimethylamine 0.00067 0.79 0.00250 0.94
   Cervonyl carnitine 0.00250 0.63 0.00115 0.54
   Betaine citrate 0.00932 0.61 0.01123 0.61
   Beta-cyclohexyl-alanine 0.00708 0.58 0.00250 0.81
   3-Ureidoisobutyric acid AND/OR alanylglycine 0.00035 0.53 0.00016 0.45
   Propenoate AND/OR alanine AND/OR beta-alanine AND/OR sarcosine 0.04694 0.52 0.00150 0.80
   Creatinine 0.00035 0.48 0.00016 0.59
   N-(3-Phenyl-2-sulfanylpropanoyl)phenylalanylalanine 0.00067 0.48 0.00016 0.56
   Creatine 0.03798 0.45 0.00016 0.48
   N1-Methyl-2-pyridone-5-carboxamide 0.00270 0.43 0.00109 0.47
   All trans decaprenyl diphosphate 0.03389 0.42 0.00114 0.40
   2-Methyl-5-hydroxytryptamine AND/OR 5-methoxytryptamine AND/OR cytisine AND/OR N-methylserotonin 0.01255 0.39 0.00021 0.58
   Dehydroisocoproporphyrinogen 0.00035 0.36 0.00220 0.23
   5-Amino-5-deoxy-cellobiono-1,5-Lactam;6-(alpha-D-glucosaminyl)-1D-myo-inositol;6-(alpha-D-glucosaminyl)-1D-myo-inositol 0.04331 0.31 0.00815 0.71
   7,8,7',8'-Tetradehydroastaxanthin 0.00035 0.23 0.00029 0.57
  1. The metabolites are separated into functional classes and arranged in order of fold change of metabolite in study 1. Where multiple metabolic features were reported for a single metabolite the feature with the P-value nearest 1 in study 1 is reported. For multiple metabolite identifications for a single metabolic feature, each unique metabolite is separated by AND/OR. The total carbon number and the number of double bonds are indicated for lysophospholipids, phospholipids and sphingomyelins. DG, diacylglycerol; dm, demethyl; PC, glycerophosphatidylcholine; PE, glycerophosphatidylethanolamine; PE-NMe, monomethylphosphatidylethanolamine; SM, sphingomyelin.
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