MetaboLightsapplication/xmlftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14089/m_MTBLS14089_GC-MS_positive__metabolite_profiling_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14089/s_MTBLS14089.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14089/a_MTBLS14089_GC-MS_positive__metabolite_profiling.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14089/i_Investigation.txtprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14089<p>Data recording was in MRM mode using the cell specific selection of the Shimadzu Smart Metabolite Database.</p>MetaboLightsPublicGas Chromatography MS - positive<p>For GC/MS analysis, a Shimadzu GC-MS/MS-system (TQ8040-NX) was used fitted with a Rxi-5Sil MS column (30 meter x 0.25 mm x 0.25 µm; Restek Corporation, Bellefonte). The GC was operated with an injection temperature of 280 °C and 1 µL sample was injected with a split of 60. The GC temperature program started with a 1&nbsp;min hold at 65 °C followed by a 6 °C/min ramp up to 220 °C, a 20 °C/min ramp up to 330 °C and a bake-out at 330 °C for 5 min, using Helium as carrier gas with constant linear velocity. </p>The accumulation of methylglyoxal and acrolein leads to arginine depletion causing hyperglycemia and renal abnormalities.Shu LiMannhein Faculty Heidelberg UniversityWhole Organismmass spectrometry assay<p>Frozen sample material was extracted with 180 µL 100% methanol containing 10 µL 0.02 mg/ml Ribitol for 15 min. at 70°C with vigorous shaking. After the addition of 100 µL 100% chloroform, samples were shaken at 37°C for 5 min. To separate polar and organic phases, 200 µL HPLC-grade water were added and samples were centrifuged for 10 min at 11,000x g. While avoiding the interphase containing cellular debris, 300 µL of the polar (upper) phase were transferred to a fresh glass vial and dried using a vacuum concentrator (Eppendorf Concentrator Plus) without heating.</p>Danio reriohttps://www.ebi.ac.uk/metabolights/MTBLS14089Shu Li. Mannhein Faculty Heidelberg University. shuli3210@163.com.Kroll Jens. Heidelberg University. Jens.Kroll@medma.uni-heidelberg.de.<p>Data recording was in MRM mode using the cell specific selection of the Shimadzu Smart Metabolite Database (see 'compounds'). The Shimadzu LabSolution Insight software was used for data processing.&nbsp;</p>Genetic manipulationshuli3210@163.com<p>The samples are zebrafish larvae at 4dpf. There are 4 groups (WT, GLO1 KO, AKR1A1A KO, GLO1/AKR1A1A DKO). Each samples has 80 larvae inside.</p>MetabolomicsMulti-omics studytargeted metabolite profilingDiabetes MellitusMulti-omics studytargeted metabolite profilingDiabetes Mellitus<p>The mass spectrometer was operated with the ion source at 200 °C and the interface at 280 °C, a solvent cut time of 4.5 min.</p>D-FructoseSucroseL-2-aminoadipic acidD-Ribulose 5-phosphateNicotinic acidDihydroxyacetone phosphateGlucaric acidO-PhosphoethanolamineGlyceraldehyde 3-phosphateL-OrnithineL-IsoleucineGlucose 6-phosphateL-Threonineglycolic acidglycineMaleic acidMalic acidCytosine¦Ã-aminobutyric acid3-Phosphoglyceric acidGlyceric acidcis-aconitic acidL-HistidineL-LeucinePyridoxalD-Mannose 6-phosphate4-Hydroxybenzoic acidGlycerol5-oxo-L-proline5-MethoxytryptamineN-acetyl-L-aspartic acidL-ProlineL-MethionineRibitolOxalic acidSuccinic acidL-Aspartic acidD-arabinitolHypoxanthineL-LysineGalacturonic acidpyruvic acidD-Gluconic acid(S)-2-hydroxyglutaric acidD-Glucose5,6-dihydrouracilTrehalosePutrescineL-Tartaric acidGuanineL-AsparagineIsocitric acid2-Aminobutyric acidethanolamine2-oxoglutaric acid¦Â-D-glucosamineGlutaric acidL-Tryptophanalanine2-Hydroxybutyric acidCystamineIsoleucineCreatinineL-Glutamic acid5-aminopentanoic acidNiacinamideL-Ascorbic acid9H-XanthineAdenosinePhosphoenolpyruvic acid(S)-Lactic acid2-hydroxyisobutyric acidPhenylalanineGlycerol 2-phosphateThymineAdenineThreonic acid3-Methyl-2-oxovaleric acid3-Hydroxypropionic acidCitric acidCholesterolXylitolL-GlutamineL-TyrosineFumaric acidOleamideL-Serinetrans-4-hydroxy-L-prolineL-ValineUracilerythritolO-phospho-L-serineN-Acetylneuraminic acid(R)-pantothenic acidfalseThe accumulation of methylglyoxal and acrolein leads to arginine depletion causing hyperglycemia and renal abnormalities<p>There is growing evidence to support the idea that the accumulation of reactive carbonyl species plays a significant causal role in the pathogenesis of ageing, cardiovascular diseases, diabetes and its complications. Among reactive carbonyl species, methylglyoxal and acrolein, detoxified by glyoxalase 1 and aldo-keto reductase 1A1A, could modify arginine residues to form the advanced glycation end products and acrolein-derived guanidino adducts that alter protein structure and function. However, it remained unclear whether the combined loss of glyoxalase 1 and aldo-keto reductase 1A1A impairs arginine metabolism and exacerbates hyperglycemia and its complications. In this study, we generated glyoxalase 1 and aldo-keto reductase 1A1A double knockout zebrafish to explore the interplay between carbonyl detoxification and arginine metabolism. Loss of both enzymes lead to accumulation of methylglyoxal and acrolein, suppression of the arginine metabolic pathway, and downregulation of insulin signaling. Double mutants exhibit elevated whole-body glucose in larvae and postprandial hyperglycemia in adults, accompanied by glomerular basement membrane thickening, while retinal vasculature remain unaffected. Remarkably, arginine supplementation restore protein kinase B/Akt phosphorylation, enhance insulin signaling, and alleviate renal pathology. Together, these findings identify glyoxalase 1 and aldo-keto reductase 1A1A as cooperative regulators of carbonyl detoxification and metabolic homeostasis. Disruption of this dual detoxification system links carbonyl stress to impaired insulin signaling and organ-specific damage through dysregulated arginine metabolism. These results uncover a carbonyl–arginine metabolic axis through which reactive carbonyl species, shaped by the synergistic activity of glyoxalase 1 and aldo-keto reductase 1A1A, drive glucose dysregulation and tissue-specific injury, highlighting potential targets for metabolic intervention in diabetes and metabolic diseases.</p>2026-06-172026-03-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:32816CHEBI:422CHEBI:50129CHEBI:17497CHEBI:16449CHEBI:15428CHEBI:16995CHEBI:1148CHEBI:33404CHEBI:35621CHEBI:17191CHEBI:35932CHEBI:16414CHEBI:17115CHEBI:16000CHEBI:15603CHEBI:17754CHEBI:15940CHEBI:17203CHEBI:18300CHEBI:15741CHEBI:33508CHEBI:17568CHEBI:18012CHEBI:16857CHEBI:17821CHEBI:17859CHEBI:15901CHEBI:17154CHEBI:6650CHEBI:17113CHEBI:16643CHEBI:18183CHEBI:16040CHEBI:17053CHEBI:18095CHEBI:16865CHEBI:16737CHEBI:26984CHEBI:30915CHEBI:32797CHEBI:17553CHEBI:44897CHEBI:16015CHEBI:28044CHEBI:30763CHEBI:15887CHEBI:15671CHEBI:21547CHEBI:17196CHEBI:17151CHEBI:18333CHEBI:17270CHEBI:15963CHEBI:37023CHEBI:17148CHEBI:32805CHEBI:15729CHEBI:17138CHEBI:16108CHEBI:18050CHEBI:17368CHEBI:17050CHEBI:30769CHEBI:30887CHEBI:15811CHEBI:16708CHEBI:17310CHEBI:15824CHEBI:17634CHEBI:28393CHEBI:18019CHEBI:17895CHEBI:15971CHEBI:17301CHEBI:29073CHEBI:46905CHEBI:33198CHEBI:33830CHEBI:17712CHEBI:16235CHEBI:17363CHEBI:16828CHEBI:78757CHEBI:4170CHEBI:17369CHEBI:116314CHEBI:2089CHEBI:17012CHEBI:16335CHEBI:17992CHEBI:16551CHEBI:16113