ArticleAmerican journal of physiology. Renal physiology2014
Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06648876 (Pharmacokinetic and Pharmacodynamics of YG1699 in Patients With Diabetes and Kidney Dysfunction), which is not on this map. Cited by 171 papers, 3 of them syntheses that pooled it.
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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.
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.
Pharmacokinetic and Pharmacodynamics of YG1699 in Patients With Diabetes and Kidney Dysfunction
Who cites it
171 citing papers in PubMed, 3 syntheses or guidelines pooled it, 296 citations in OpenAlex.
- iCatCare 2025 consensus guidelines on the diagnosis and management of diabetes mellitus in cats.Journal of feline medicine and surgery · 2025Guideline
- Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review.Journal of diabetes research · 2020Pooled it
- Pooled it
- Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial.Clinical journal of the American Society of Nephrology : CJASN · 2021Trial
- Pharmacokinetic and pharmacodynamic modelling for renal function dependent urinary glucose excretion effect of ipragliflozin, a selective sodium-glucose cotransporter 2 inhibitor, both in healthy subjects and patients with type 2 diabetes mellitus.British journal of clinical pharmacology · 2019Trial
- Dapagliflozin Beyond Glucose Lowering: Mechanisms of Renal and Systemic Protection.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- SGLT2 gene expression in thirst-promoting NOS1 neurons and vasopressin-synthesizing neurons in male rats.Physiological reports · 2026Article
- The Potential Role of SGLT2 Inhibitors in Cushing's Disease.Diabetes, obesity & metabolism · 2026Review
- Transcriptomics of S3 segment in mice: response to type 1 diabetes, SGLT1/2 inhibition, or GLP1 receptor agonism.American journal of physiology. Renal physiology · 2026Article
- Pharmacokinetics of Ertugliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor (SGLT2i) in Horses After Enteral Administration.Veterinary sciences · 2026Article
- Age-Related Adaptations in Renal Tubular Function in Female Rats.Acta physiologica (Oxford, England) · 2026Article
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- Cellular microenvironment of erythropoietin-producing cells in hypoxic and injured mouse kidneys.Experimental physiology · 2026Article
- Sodium-Glucose Cotransporter 2 Inhibitors in Autosomal Dominant Polycystic Kidney Disease: Mechanistic Insights and Therapeutic Promise.Journal of the American Society of Nephrology : JASN · 2026Review
- Repurposing SGLT2 Inhibitors for Cirrhotic Ascites: From Mechanistic Research to Clinical Exploration.Journal of clinical and translational hepatology · 2026Review
- Canagliflozin treatment of a horse with hyperinsulinemia, including pharmacokinetic analysis of different dosing protocols: a case report.Frontiers in veterinary science · 2026Article
- Sodium-glucose transporters SGLT1 and SGLT2 in equine renal, hepatic and pancreatic tissue.BMC veterinary research · 2025Article
- The impact of initiating SGLT2 inhibitors on eGFR: a pilot study at a secondary hospital in Malaysia.BMC research notes · 2025Article
- Complementary Yet Distinct Roles of GLP-1 Receptor Agonists and SGLT2 Inhibitors in Cardiovascular Risk Reduction.Biomedicines · 2025Review
- Modern antidiabetic therapy by sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors against cardiovascular diseases.Pharmacological reviews · 2025Review
111 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40-50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the maximum response doubled in Sglt1 knockout (Sglt1-/-) mice. Treatment in diet with the SGLT2-I for 3 wk maintained 1.5- to 2-fold higher urine glucose/creatinine ratios in Sglt1-/- vs. WT mice, associated with a temporarily greater reduction in blood glucose in Sglt1-/- vs. WT after 24 h (-33 vs. -11%). Subsequent inulin clearance studies under anesthesia revealed free plasma concentrations of the SGLT2-I (corresponding to early proximal concentration) close to the reported IC50 for SGLT2 in mice, which were associated with FGR of 64 ± 2% in WT and 17 ± 2% in Sglt1-/-. Additional intraperitoneal application of the SGLT2-I (maximum effective dose in metabolic cages) increased free plasma concentrations ∼10-fold and reduced FGR to 44 ± 3% in WT and to -1 ± 3% in Sglt1-/-. The absence of renal glucose reabsorption was confirmed in male and female Sglt1/Sglt2 double knockout mice. In conclusion, SGLT2 and SGLT1 account for renal glucose reabsorption in euglycemia, with 97 and 3% being reabsorbed by SGLT2 and SGLT1, respectively. When SGLT2 is fully inhibited by SGLT2-I, the increase in SGLT1-mediated glucose reabsorption explains why only 50-60% of filtered glucose is excreted.
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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.