ArticleAmerican journal of physiology. Renal physiology2016
Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron.
Article in American journal of physiology. Renal physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
- Pooled it
- Effect of empagliflozin on urinary albumin excretion and hypoxic biomarkers in early diabetic kidney disease: A randomised double-blind, placebo-controlled trial.Diabetes, obesity & metabolism · 2026Trial
- Trial
- Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial.Diabetologia · 2023Trial
- Empagliflozin confers reno-protection in acute myocardial infarction and type 2 diabetes mellitus.ESC heart failure · 2021Trial
- Renal effects of a sodium-glucose cotransporter 2 inhibitor, tofogliflozin, in relation to sodium intake and glycaemic status.Diabetes, obesity & metabolism · 2019Trial
- Timing-dependent renal protection of dapagliflozin in endotoxemic diabetic mice by real-time GFR and biomarkers.Intensive care medicine experimental · 2026Article
- Hypoxia inducible factor network reflects kidney disease progression in diabetes and sodium-glucose co-transporters inhibition.Signal transduction and targeted therapy · 2026Article
- Sweet relief: exploring mechanisms and therapeutic approaches of sodium-glucose cotransporter-2 inhibitors in cardiovascular-kidney metabolic syndrome.Cardiovascular diabetology · 2026Review
- Zinc, type 2 diabetes, diabetic kidney disease: focus on hypoxia.Frontiers in endocrinology · 2026Review
- SGLT2 Inhibitors: Multifaceted Therapeutic Agents in Cardiometabolic and Renal Diseases.Metabolites · 2025Review
- Renal handling of albumin in rats with early stage diabetes: A theoretical analysis.The Journal of physiology · 2024Article
- SGLT2-independent effects of canagliflozin on NHE3 and mitochondrial complex I activity inhibit proximal tubule fluid transport and albumin uptake.American journal of physiology. Renal physiology · 2024Article
- How the kidney regulates magnesium: a modelling study.Royal Society open science · 2024Article
- Sex differences in renal transporters: assessment and functional consequences.Nature reviews. Nephrology · 2024Review
- Mechanisms of enhanced renal and hepatic erythropoietin synthesis by sodium-glucose cotransporter 2 inhibitors.European heart journal · 2023Article
- Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia.Antioxidants (Basel, Switzerland) · 2023Review
- Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes.Circulation · 2023Review
- SGLT2 inhibitors, intrarenal hypoxia and the diabetic kidney: insights into pathophysiological concepts and current evidence.Archives of medical sciences. Atherosclerotic diseases · 2023Article
- Empagliflozin increases kidney weight due to increased cell size in the proximal tubule S3 segment and the collecting duct.Frontiers in pharmacology · 2023Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Diabetes increases the reabsorption of Na(+) (TNa) and glucose via the sodium-glucose cotransporter SGLT2 in the early proximal tubule (S1-S2 segments) of the renal cortex. SGLT2 inhibitors enhance glucose excretion and lower hyperglycemia in diabetes. We aimed to investigate how diabetes and SGLT2 inhibition affect TNa and sodium transport-dependent oxygen consumption [Formula: see text] along the whole nephron. To do so, we developed a mathematical model of water and solute transport from the Bowman space to the papillary tip of a superficial nephron of the rat kidney. Model simulations indicate that, in the nondiabetic kidney, acute and chronic SGLT2 inhibition enhances active TNa in all nephron segments, thereby raising [Formula: see text] by 5-12% in the cortex and medulla. Diabetes increases overall TNa and [Formula: see text] by ∼50 and 100%, mainly because it enhances glomerular filtration rate (GFR) and transport load. In diabetes, acute and chronic SGLT2 inhibition lowers [Formula: see text] in the cortex by ∼30%, due to GFR reduction that lowers proximal tubule active TNa, but raises [Formula: see text] in the medulla by ∼7%. In the medulla specifically, chronic SGLT2 inhibition is predicted to increase [Formula: see text] by 26% in late proximal tubules (S3 segments), by 2% in medullary thick ascending limbs (mTAL), and by 9 and 21% in outer and inner medullary collecting ducts (OMCD and IMCD), respectively. Additional blockade of SGLT1 in S3 segments enhances glucose excretion, reduces [Formula: see text] by 33% in S3 segments, and raises [Formula: see text] by <1% in mTAL, OMCD, and IMCD. In summary, the model predicts that SGLT2 blockade in diabetes lowers cortical [Formula: see text] and raises medullary [Formula: see text], particularly in S3 segments.
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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.