ArticleJCI insight2023
Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Distinct metabolomic signatures of SGLT2 inhibitor vs. sulfonylurea in a paired human liver biopsy study.Biochemistry and biophysics reports · 2026Article
- SGLT2 inhibitors: mechanisms, physiology and pharmacology, and clinical applications.Molecular biomedicine · 2026Review
- Renal glycosuria triggers a coordinated mannose and glutamine metabolic program to maintain glucose homeostasis.Cell reports · 2026Article
- Review
- CD59 drives diet-induced obesity and glucose intolerance, insulin resistance, and metabolic dysfunction-associated steatotic liver disease.npj metabolic health and disease · 2026Article
- Glucosamine links hyperglycemia to mTORC1 activation and glucose toxicity in diabetes.JCI insight · 2026Article
- Metabolic Reprogramming Coordinates Mannose and Glutamine Metabolism to Maintain Glucose Homeostasis During Glycosuria.bioRxiv : the preprint server for biology · 2026Article
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- Dapagliflozin regulates chondrocyte homeostasis and protects against osteoarthritis via targets AMPKα and SGLT2.Cell death discovery · 2026Article
- The SGLT2 inhibitor empagliflozin promotes increased fatty acid oxidation in skeletal muscle cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- SGLT2 inhibitors and acute kidney injury.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Review
- Metabolomics for Preclinical Detection of Diabetic Kidney Disease: A Comprehensive Review.International journal of molecular sciences · 2026Review
- Systemic effects of type 2 diabetes therapies: an integrated perspective on the cardio-renal- cerebral-metabolic axis.Frontiers in medicine · 2026Review
- Nephroprotective Mechanisms of SGLT2i: Beyond the Glucose-Lowering Effect.Biomedicines · 2025Review
- Metabolic consequences of altered kidney glucose reabsorption under normoglycemic conditions.Molecular metabolism · 2025Article
- Risk of colorectal cancer and cancer-related mortality in type 2 diabetes patients treated with metformin, SGLT-2 inhibitors, or their combination.Cancer communications (London, England) · 2025Article
- METTL3 mediates atheroprone flow-induced glycolysis in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment.Cells · 2024Review
- Duality of Branched-Chain Amino Acids in Chronic Cardiovascular Disease: Potential Biomarkers versus Active Pathophysiological Promoters.Nutrients · 2024Review
- Sodium-glucose cotransporter-2 inhibitors protect tissuesWorld journal of experimental medicine · 2024Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Diabetes is associated with increased risk for kidney disease, heart failure, and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent these adverse outcomes; however, the mechanisms involved are not clear. We generated a roadmap of the metabolic alterations that occur in different organs in diabetes and in response to SGLT2i. In vivo metabolic labeling with 13C-glucose in normoglycemic and diabetic mice treated with or without dapagliflozin, followed by metabolomics and metabolic flux analyses, showed that, in diabetes, glycolysis and glucose oxidation are impaired in the kidney, liver, and heart. Treatment with dapagliflozin failed to rescue glycolysis. SGLT2 inhibition increased glucose oxidation in all organs; in the kidney, this was associated with modulation of the redox state. Diabetes was associated with altered methionine cycle metabolism, evident by decreased betaine and methionine levels, whereas treatment with SGLT2i increased hepatic betaine along with decreased homocysteine levels. mTORC1 activity was inhibited by SGLT2i along with stimulation of AMPK in both normoglycemic and diabetic animals, possibly explaining the protective effects against kidney, liver, and heart diseases. Collectively, our findings suggest that SGLT2i induces metabolic reprogramming orchestrated by AMPK-mTORC1 signaling with common and distinct effects in various tissues, with implications for diabetes and aging.
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