ArticleThe Journal of clinical investigation2023
SGLT2 inhibitors mitigate kidney tubular metabolic and mTORC1 perturbations in youth-onset type 2 diabetes.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07175051 (Targeting the Pathophysiology of Sickle Cell-Related Kidney Disease Using the SGLT2 Inhibitors, Empagliflozin), which is not on this map. Cited by 71 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Targeting the Pathophysiology of Sickle Cell-Related Kidney Disease Using the SGLT2 Inhibitors, Empagliflozin
Who cites it
71 citing papers in PubMed, 98 citations in OpenAlex.
- Association of Urinary EGF with Kidney Outcomes and Effects of Sodium-Glucose Cotransporter 2 Inhibition.Journal of the American Society of Nephrology : JASN · 2026Trial
- Metabolic surgery mitigates early kidney injury in obese youth with diabetes by suppressing mTORC1/JAK/STAT signaling.The Journal of clinical investigation · 2026Trial
- Trial
- Adjunct-to-insulin therapy using SGLT2 inhibitors in youth with type 1 diabetes: a randomized controlled trial.Nature medicine · 2025Trial
- SGLT2 inhibitors: mechanisms, physiology and pharmacology, and clinical applications.Molecular biomedicine · 2026Review
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Not all reference samples are equal in single-cell transcriptomics of human kidney tissue.JCI insight · 2026Article
- A MEF2C transcription factor network regulates proliferation of glomerular endothelial cells in diabetic kidney disease.Kidney international · 2026Article
- Review
- Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Kidney-Vascular Metabolic Crosstalk: Altered Lipoproteins in CKD.Circulation research · 2026Review
- SGLT2 inhibition with empagliflozin attenuates retinal oxidative stress and damage in diabetic mice.Scientific reports · 2026Article
- Hypoxia inducible factor network reflects kidney disease progression in diabetes and sodium-glucose co-transporters inhibition.Signal transduction and targeted therapy · 2026Article
- Shared multicellular injury programs of acute and chronic kidney disease enable mechanistic patient stratification.medRxiv : the preprint server for health sciences · 2026Article
- Spatial metabolomics and multiomics integration for breakthroughs in precision medicine for kidney disease.Nature reviews. Nephrology · 2026Review
- Impact of Empagliflozin on Glomerular Hyperfiltration and Albuminuria in Youth with Type 2 Diabetes: Post Hoc Analysis of DINAMO.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Chronic Kidney Disease in Metabolic Disease: Regulation of SGLT2 and Transcriptomic-Epigenetic Effects of Its Pharmacological Inhibition.International journal of molecular sciences · 2026Review
- AMPK-OXSR1 signaling coordinates proximal tubular sodium transport and is modulated by canagliflozin.Frontiers in endocrinology · 2026Article
- A Holistic Approach to AKI: Integrating Clinical and Molecular Data in the Human Kidney.Seminars in nephrology · 2025Review
- Rationale, design and baseline characteristics of REMODEL, a mechanism-of-action trial with semaglutide in people with type 2 diabetes and chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
The molecular mechanisms of sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) remain incompletely understood. Single-cell RNA sequencing and morphometric data were collected from research kidney biopsies donated by young persons with type 2 diabetes (T2D), aged 12 to 21 years, and healthy controls (HCs). Participants with T2D were obese and had higher estimated glomerular filtration rates and mesangial and glomerular volumes than HCs. Ten T2D participants had been prescribed SGLT2i (T2Di[+]) and 6 not (T2Di[-]). Transcriptional profiles showed SGLT2 expression exclusively in the proximal tubular (PT) cluster with highest expression in T2Di(-) patients. However, transcriptional alterations with SGLT2i treatment were seen across nephron segments, particularly in the distal nephron. SGLT2i treatment was associated with suppression of transcripts in the glycolysis, gluconeogenesis, and tricarboxylic acid cycle pathways in PT, but had the opposite effect in thick ascending limb. Transcripts in the energy-sensitive mTORC1-signaling pathway returned toward HC levels in all tubular segments in T2Di(+), consistent with a diabetes mouse model treated with SGLT2i. Decreased levels of phosphorylated S6 protein in proximal and distal tubules in T2Di(+) patients confirmed changes in mTORC1 pathway activity. We propose that SGLT2i treatment benefits the kidneys by mitigating diabetes-induced metabolic perturbations via suppression of mTORC1 signaling in kidney tubules.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.