Evidence mapPaperPMID 30867247Full record

ArticleJournal of the American Society of Nephrology : JASN2019

Macula Densa SGLT1-NOS1-Tubuloglomerular Feedback Pathway, a New Mechanism for Glomerular Hyperfiltration during Hyperglycemia.

Jie Zhang, Jin Wei, Shan Jiang, Lan Xu, Lei Wang, Feng Cheng, Jacentha Buggs, Hermann Koepsell, Volker Vallon, Ruisheng Liu

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
8.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 97 citations in OpenAlex.

  1. Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial.Clinical journal of the American Society of Nephrology : CJASN · 2021
    Trial
  2. Article
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  4. Chronic NHScientific reports · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Gliflozins in hypertension: basic mechanisms and clinical insights.American journal of physiology. Renal physiology · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Acute Kidney Injury by Ischemia/Reperfusion and Extracellular Vesicles.International journal of molecular sciences · 2023
    Review
  18. Role of Alström syndrome 1 in the regulation of glomerular hemodynamics.American journal of physiology. Renal physiology · 2023
    Article
  19. Renal Oxygen Demand and Nephron Function: Is Glucose a Friend or Foe?International journal of molecular sciences · 2023
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Jie ZhangDepartment of Molecular Pharmacology and Physiology, College of Medicine, jzhang10@health.usf.edu.
Jin WeiDepartment of Molecular Pharmacology and Physiology, College of Medicine.
Shan JiangDepartment of Molecular Pharmacology and Physiology, College of Medicine.
Lan XuDepartment of Biostatistics, College of Public Health, and.
Lei WangDepartment of Molecular Pharmacology and Physiology, College of Medicine.
Feng ChengDepartment of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, Florida.
Jacentha BuggsAdvanced Organ Disease & Transplantation Institute, Tampa General Hospital, Tampa, Florida.
Hermann KoepsellInstitute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany; and.
Volker VallonDivision of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, La Jolla, California.
Ruisheng LiuDepartment of Molecular Pharmacology and Physiology, College of Medicine.
Tampa General Hospital · USUniversity of California, San Diego · USUniversity of South Florida · USUniversity of Würzburg · DE

Funding

Glomerular and Tubular Function in the Diabetic KidneyR01DK112042 · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · 2025 to 2025
$475k
NHLBI NIH HHS R01 HL137987NHLBI NIH HHS R01 HL142814NIDDK NIH HHS R01 DK099276NIDDK NIH HHS R01 DK106102NIDDK NIH HHS R01 DK112042
6 · The paper itself

Abstract

backgroundGlomerular hyperfiltration is common in early diabetes and is considered a risk factor for later diabetic nephropathy. We propose that sodium-glucose cotransporter 1 (SGLT1) senses increases in luminal glucose at the macula densa, enhancing generation of neuronal nitric oxide synthase 1 (NOS1)-dependent nitric oxide (NO) in the macula densa and blunting the tubuloglomerular feedback (TGF) response, thereby promoting the rise in GFR.

methodsWe used microperfusion, micropuncture, and renal clearance of FITC-inulin to examine the effects of tubular glucose on NO generation at the macula densa, TGF, and GFR in wild-type and macula densa-specific NOS1 knockout mice.

resultsAcute intravenous injection of glucose induced hyperglycemia and glucosuria with increased GFR in mice. We found that tubular glucose blunts the TGF response

conclusionsWe identified a novel mechanism of acute hyperglycemia-induced hyperfiltration wherein increases in luminal glucose at the macula densa upregulate the expression and activity of NOS1

Indexed as

AnimalsFeedback, PhysiologicalGlomerular Filtration RateGlucoseGlucosidesHumansHyperglycemiaInulinKidney GlomerulusKidney Tubules, DistalMaleMiceMice, KnockoutNitric OxideNitric Oxide Synthase Type IPhosphorylation3-(3-(4-(3-(glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl)-3-methylphenoxy)propylamino)propionamideGlucoseGlucosidesInulinNitric OxideNitric Oxide Synthase Type INOS1 protein, humanNos1 protein, mousePyrazolesSlc5a1 protein, mouseSodium-Glucose Transporter 1glomerular hyperfiltrationhyperglycemiaNOS1SGLT1tubuloglomerular feedback

Identifiers

PMID30867247
PMCPMC6442354
OpenAlexW2922268276

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.