Evidence map›Paper›PMID 34843754›Full record

ArticleKidney international2022

Role of the macula densa sodium glucose cotransporter type 1-neuronal nitric oxide synthase-tubuloglomerular feedback pathway in diabetic hyperfiltration.

Jie Zhang, Jing Cai, Yu Cui, Shan Jiang, Jin Wei, Young Chul Kim, Jenna Chan, Anish Thalakola, Thanh Le, Lan Xu and 9 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Gliflozins in hypertension: basic mechanisms and clinical insights.American journal of physiology. Renal physiology · 2025
    Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Tubuloglomerular feedback: a key player in obesity-associated kidney injury.American journal of physiology. Renal physiology · 2022
    Article
  14. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 3 countries.

Jie ZhangDepartment of Molecular Pharmacology & Physiology, College of Medicine, University of South Florida, Tampa, Florida, USA. Electronic address: jzhang10@usf.edu.
Jing CaiDepartment of Otolarynggology-Head and Neck Surgery, Cheeloo College of Medicine, Shandong University, Jinan, China.
Yu CuiKidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Shan JiangDepartment of Molecular Pharmacology & Physiology, College of Medicine, University of South Florida, Tampa, Florida, USA.
Jin WeiDepartment of Molecular Pharmacology & Physiology, College of Medicine, University of South Florida, Tampa, Florida, USA.
Young Chul KimDivision of Nephrology and Hypertension, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Jenna ChanDepartment of Molecular Pharmacology & Physiology, College of Medicine, University of South Florida, Tampa, Florida, USA.
Anish ThalakolaDepartment of Molecular Pharmacology & Physiology, College of Medicine, University of South Florida, Tampa, Florida, USA.
Thanh LeDepartment of Molecular Pharmacology & Physiology, College of Medicine, University of South Florida, Tampa, Florida, USA.
Lan XuCollege of Public Health, University of South Florida, Tampa, Florida, USA.
Lei WangDepartment of Molecular Pharmacology & Physiology, College of Medicine, University of South Florida, Tampa, Florida, USA.
Kun JiangDepartment of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Ximing WangDepartment of Molecular Pharmacology & Physiology, College of Medicine, University of South Florida, Tampa, Florida, USA.
Haibo WangDepartment of Otolarynggology-Head and Neck Surgery, Cheeloo College of Medicine, Shandong University, Jinan, China.
Feng ChengDepartment of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, Florida, USA.
Jacentha BuggsAdvanced Organ Disease & Transplantation Institute, Tampa General Hospital, Tampa, Florida, USA.
Hermann KoepsellInstitute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
Volker VallonDivision of Nephrology and Hypertension, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Ruisheng LiuDepartment of Molecular Pharmacology & Physiology, College of Medicine, University of South Florida, Tampa, Florida, USA.
University of South Florida · USShandong University · CNUniversity of California San Diego · USMoffitt Cancer Center · USTampa General Hospital · USUniversity of Würzburg · DEZhejiang University · CN

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 DK106102NIDDK NIH HHS R01 DK112042NIDDK NIH HHS R01 DK122050
6 · The paper itself

Abstract

An increase of glomerular filtration rate (GFR) is a common observation in early diabetes and is considered a key risk factor for subsequent kidney injury. However, the mechanisms underlying diabetic hyperfiltration have not been fully clarified. Here, we tested the hypothesis that macula densa neuronal nitric oxide synthase (NOS1) is upregulated via sodium glucose cotransporter type 1 (SGLT1) in diabetes, which then inhibits tubuloglomerular feedback (TGF) promoting glomerular hyperfiltration. Therefore, we examined changes in cortical NOS1 expression and phosphorylation, nitric oxide production in the macula densa, TGF response, and GFR during the early stage of insulin-deficient (Akita) diabetes in wild-type and macula densa-specific NOS1 knockout mice. A set of sophisticated techniques including microperfusion of juxtaglomerular apparatus in vitro, micropuncture of kidney tubules in vivo, and clearance kinetics of plasma fluorescent-sinistrin were employed. Complementary studies tested the role of SGLT1 in SGLT1 knockout mice and explored NOS1 expression and phosphorylation in kidney biopsies of cadaveric donors. Diabetic mice had upregulated macula densa NOS1, inhibited TGF and elevated GFR. Macula densa-selective NOS1 knockout attenuated the diabetes-induced TGF inhibition and GFR elevation. Additionally, deletion of SGLT1 prevented the upregulation of macula densa NOS1 and attenuated inhibition of TGF in diabetic mice. Furthermore, the expression and phosphorylation levels of NOS1 were increased in cadaveric kidneys of diabetics and positively correlated with blood glucose as well as estimated GFR in the donors. Thus, our findings demonstrate that the macula densa SGLT1-NOS1-TGF pathway plays a crucial role in the control of GFR in diabetes.

Indexed as

Diabetes Mellitus, ExperimentalAnimalsFeedbackGlomerular Filtration RateKidney GlomerulusKidney TubulesMiceNitric OxideNitric Oxide Synthase Type ISodium-Glucose Transporter 1Nitric OxideNitric Oxide Synthase Type ISlc5a1 protein, mouseSodium-Glucose Transporter 1diabetesglomerular filtration rateneuronal nitric oxide synthaserenal hemodynamicsodium glucose cotransporter type 1tubuloglomerular feedback

Identifiers

PMID34843754
PMCPMC8863629
OpenAlexW3215872583

What Socratic holds

Textmetadata
LicenceTDM
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.