ArticleThe Journal of biological chemistry2017
SGLT2 Protein Expression Is Increased in Human Diabetic Nephropathy: SGLT2 PROTEIN INHIBITION DECREASES RENAL LIPID ACCUMULATION, INFLAMMATION, AND THE DEVELOPMENT OF NEPHROPATHY IN DIABETIC MICE.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers, 3 of them syntheses that pooled it.
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Who cites it
172 citing papers in PubMed, 3 syntheses or guidelines pooled it, 296 citations in OpenAlex.
- Approach to Studies on Podocyte Lesions Mediated by Hyperglycemia: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Optimizing diabetic kidney disease animal models: Insights from a meta-analytic approach.Animal models and experimental medicine · 2023Pooled it
- Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review.Journal of diabetes research · 2020Pooled it
- Short- and mid-term effects of empagliflozin on sodium balance and fluid regulation in chronic heart failure.European journal of heart failure · 2025Trial
- Effect of Dapagliflozin on Renal and Hepatic Glucose Kinetics in T2D and NGT Subjects.Diabetes · 2024Trial
- Effect of Canagliflozin on Renal and Cardiovascular Outcomes across Different Levels of Albuminuria: Data from the CANVAS Program.Journal of the American Society of Nephrology : JASN · 2019Trial
- Renal effects of a sodium-glucose cotransporter 2 inhibitor, tofogliflozin, in relation to sodium intake and glycaemic status.Diabetes, obesity & metabolism · 2019Trial
- Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study.American journal of physiology. Renal physiology · 2018Trial
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Identification of novel small molecules as potential SGLT2 inhibitors through combined virtual screening and experimental validation.Molecular diversity · 2026Article
- Sweet relief: exploring mechanisms and therapeutic approaches of sodium-glucose cotransporter-2 inhibitors in cardiovascular-kidney metabolic syndrome.Cardiovascular diabetology · 2026Review
- Neural Upregulation of SGLT2-MAP17-PDZK1 Complex in Kidneys of Rats With Heart Failure.Hypertension (Dallas, Tex. : 1979) · 2026Article
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- Dynamics and Predictive Values of Urinary Podocyte Biomarkers Following SGLT2 Inhibition in CKD.Life (Basel, Switzerland) · 2026Article
- SOCS1 Mimetic Peptide Enhances Empagliflozin Improvement on Kidney Damage in the Type 2 Diabetes Mouse Model BTBR ob/ob.International journal of molecular sciences · 2026Article
- Fibroblast growth factor 1 alleviates diabetic nephropathy by reducing renal lipid accumulation in diabetic kidney.World journal of diabetes · 2026Article
- Empagliflozin alleviates lipid deposition and inflammation in diabetic kidney disease by downregulating C1QC.Molecular and cellular biochemistry · 2026Article
- Computational Discovery of Novel SGLT2 Inhibitors from Eight Selected Medicine Food Homology Herbs Using a Multi-Stage Virtual Screening Pipeline.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Integrated causal inference, kidney transcriptomics, and experimental validation identify ChREBP (Frontiers in endocrinology · 2026Article
- SGLT2 Inhibitors and Liver Cirrhosis: Hype or Hope?Life (Basel, Switzerland) · 2025Review
112 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
There is very limited human renal sodium gradient-dependent glucose transporter protein (SGLT2) mRNA and protein expression data reported in the literature. The first aim of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice that had no changes in renal SGLT2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known. The second aim of this study was to determine the potential mechanisms of beneficial effects of SGLT2 inhibition in the progression of diabetic renal disease. We treated db/db mice with a selective SGLT2 inhibitor JNJ 39933673. We found that SGLT2 inhibition caused marked decreases in systolic blood pressure, kidney weight/body weight ratio, urinary albumin, and urinary thiobarbituric acid-reacting substances. SGLT2 inhibition prevented renal lipid accumulation via inhibition of carbohydrate-responsive element-binding protein-β, pyruvate kinase L, SCD-1, and DGAT1, key transcriptional factors and enzymes that mediate fatty acid and triglyceride synthesis. SGLT2 inhibition also prevented inflammation via inhibition of CD68 macrophage accumulation and expression of p65, TLR4, MCP-1, and osteopontin. These effects were associated with reduced mesangial expansion, accumulation of the extracellular matrix proteins fibronectin and type IV collagen, and loss of podocyte markers WT1 and synaptopodin, as determined by immunofluorescence microscopy. In summary, our study showed that SGLT2 inhibition modulates renal lipid metabolism and inflammation and prevents the development of nephropathy in db/db mice.
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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 Socratic graph.