Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
Article has an altmetric score of 16

See more details

Picked up by 1 news outlets
Posted by 1 X users
Referenced in 33 patents
157 readers on Mendeley
  • Article usage
  • Citations to this article (623)

Advertisement

Research Article Free access | 10.1172/JCI116972

The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose.

Y Kanai, W S Lee, G You, D Brown, and M A Hediger

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.

Find articles by Kanai, Y. in: JCI | PubMed | Google Scholar

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.

Find articles by Lee, W. in: JCI | PubMed | Google Scholar

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.

Find articles by You, G. in: JCI | PubMed | Google Scholar

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.

Find articles by Brown, D. in: JCI | PubMed | Google Scholar

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.

Find articles by Hediger, M. in: JCI | PubMed | Google Scholar

Published January 1, 1994 - More info

Published in Volume 93, Issue 1 on January 1, 1994
J Clin Invest. 1994;93(1):397–404. https://doi.org/10.1172/JCI116972.
© 1994 The American Society for Clinical Investigation
Published January 1, 1994 - Version history
View PDF
Abstract

The major reabsorptive mechanism for D-glucose in the kidney is known to involve a low affinity high capacity Na+/glucose cotransporter, which is located in the early proximal convoluted tubule segment S1, and which has a Na+ to glucose coupling ratio of 1:1. Here we provide the first molecular evidence for this renal D-glucose reabsorptive mechanism. We report the characterization of a previously cloned human kidney cDNA that codes for a protein with 59% identity to the high affinity Na+/glucose cotransporter (SGLT1). Using expression studies with Xenopus laevis oocytes we demonstrate that this protein (termed SGLT2) mediates saturable Na(+)-dependent and phlorizin-sensitive transport of D-glucose and alpha-methyl-D-glucopyranoside (alpha MeGlc) with Km values of 1.6 mM for alpha MeGlc and approximately 250 to 300 mM for Na+, consistent with low affinity Na+/glucose cotransport. In contrast to SGLT1, SGLT2 does not transport D-galactose. By comparing the initial rate of [14C]-alpha MeGlc uptake with the Na(+)-influx calculated from alpha MeGlc-evoked inward currents, we show that the Na+ to glucose coupling ratio of SGLT2 is 1:1. Using combined in situ hybridization and immunocytochemistry with tubule segment specific marker antibodies, we demonstrate an extremely high level of SGLT2 message in proximal tubule S1 segments. This level of expression was also evident on Northern blots and likely confers the high capacity of this glucose transport system. We conclude that SGLT2 has properties characteristic of the renal low affinity high capacity Na+/glucose cotransporter as previously reported for perfused tubule preparations and brush border membrane vesicles. Knowledge of the structural and functional properties of this major renal Na+/glucose reabsorptive mechanism will advance our understanding of the pathophysiology of renal diseases such as familial renal glycosuria and diabetic renal disorders.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 397
page 397
icon of scanned page 398
page 398
icon of scanned page 399
page 399
icon of scanned page 400
page 400
icon of scanned page 401
page 401
icon of scanned page 402
page 402
icon of scanned page 403
page 403
icon of scanned page 404
page 404
Version history
  • Version 1 (January 1, 1994): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

Article has an altmetric score of 16
  • Article usage
  • Citations to this article (623)

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 1 news outlets
Posted by 1 X users
Referenced in 33 patents
157 readers on Mendeley
See more details