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A metabolomics-based molecular pathway analysis of how the sodium-glucose co-transporter-2 inhibitor dapagliflozin may slow kidney function decline in patients with diabetes.


ABSTRACT: AIM:To investigate which metabolic pathways are targeted by the sodium-glucose co-transporter-2 inhibitor dapagliflozin to explore the molecular processes involved in its renal protective effects. METHODS:An unbiased mass spectrometry plasma metabolomics assay was performed on baseline and follow-up (week 12) samples from the EFFECT II trial in patients with type 2 diabetes with non-alcoholic fatty liver disease receiving dapagliflozin 10 mg/day (n = 19) or placebo (n = 6). Transcriptomic signatures from tubular compartments were identified from kidney biopsies collected from patients with diabetic kidney disease (DKD) (n = 17) and healthy controls (n = 30) from the European Renal cDNA Biobank. Serum metabolites that significantly changed after 12?weeks of dapagliflozin were mapped to a metabolite-protein interaction network. These proteins were then linked with intra-renal transcripts that were associated with DKD or estimated glomerular filtration rate (eGFR). The impacted metabolites and their protein-coding transcripts were analysed for enriched pathways. RESULTS:Of all measured (n = 812) metabolites, 108 changed (P?

SUBMITTER: Mulder S 

PROVIDER: S-EPMC7317707 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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A metabolomics-based molecular pathway analysis of how the sodium-glucose co-transporter-2 inhibitor dapagliflozin may slow kidney function decline in patients with diabetes.

Mulder Skander S   Hammarstedt Ann A   Nagaraj Sunil B SB   Nair Viji V   Ju Wenjun W   Hedberg Jonatan J   Greasley Peter J PJ   Eriksson Jan W JW   Oscarsson Jan J   Heerspink Hiddo J L HJL  

Diabetes, obesity & metabolism 20200325 7


<h4>Aim</h4>To investigate which metabolic pathways are targeted by the sodium-glucose co-transporter-2 inhibitor dapagliflozin to explore the molecular processes involved in its renal protective effects.<h4>Methods</h4>An unbiased mass spectrometry plasma metabolomics assay was performed on baseline and follow-up (week 12) samples from the EFFECT II trial in patients with type 2 diabetes with non-alcoholic fatty liver disease receiving dapagliflozin 10 mg/day (n = 19) or placebo (n = 6). Transc  ...[more]

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