Kidney Proximal Tubule GLUT2—More than Meets the Eye

Majdoleen Ahmad, Ifat Abramovich, Bella Agranovich, Alina Nemirovski, Eyal Gottlieb, Liad Hinden*, Joseph Tam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Tubulopathy plays a central role in the pathophysiology of diabetic kidney disease (DKD). Under diabetic conditions, the kidney proximal tubule cells (KPTCs) are exposed to an extensive amount of nutrients, most notably glucose; these nutrients deteriorate KPTCs function and promote the development and progression of DKD. Recently, the facilitative glucose transporter 2 (GLUT2) in KPTCs has emerged as a central regulator in the pathogenesis of DKD. This has been demonstrated by identifying its specific role in enhancing glucose reabsorption and glucotoxicity, and by deciphering its effect in regulating the expression of the sodium-glucose transporter 2 (SGLT2) in KPTCs. Moreover, reduction/deletion of KPTC-GLUT2 has been recently found to ameliorate DKD, raising the plausible idea of considering it as a therapeutic target against DKD. However, the underlying molecular mechanisms by which GLUT2 exerts its deleterious effects in KPTCs remain vague. Herein, we review the current findings on the proximal tubule GLUT2 biology and function under physiologic conditions, and its involvement in the pathophysiology of DKD. Furthermore, we shed new light on its cellular regulation during diabetic conditions.

Original languageAmerican English
Article number94
JournalCells
Volume12
Issue number1
DOIs
StatePublished - 26 Dec 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

  • AMPK
  • CB1R
  • GLUT2
  • KPTCs
  • SGLT2
  • SREBP1
  • diabetic kidney disease
  • importin-α1
  • mTORC1

Fingerprint

Dive into the research topics of 'Kidney Proximal Tubule GLUT2—More than Meets the Eye'. Together they form a unique fingerprint.

Cite this