Aminoglycoside antibiotics reduce glucose reabsorption in kidney through down-regulation of SGLT1

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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

Kozo Takamoto1, Manabu Kawada, Takayuki Usui

  • 1Microbial Chemistry Research Center, Numazu Bio-Medical Research Institute, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan.

Biochemical and Biophysical Research Communications
|August 21, 2003
PubMed

Insights

Aminoglycoside antibiotics harm kidneys by reducing glucose reabsorption. This study reveals that these drugs down-regulate the Na+/glucose cotransporter (SGLT1), a key protein in kidney glucose transport.

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • Aminoglycoside antibiotics are essential but can cause nephrotoxicity.
  • The precise mechanisms underlying aminoglycoside-induced kidney damage remain incompletely understood.
  • Proximal tubular cells are primary targets for aminoglycoside toxicity.

Purpose of the Study:

  • To investigate the impact of aminoglycoside antibiotics on renal glucose transport systems.
  • To elucidate the role of Na+/glucose cotransporter 1 (SGLT1) in aminoglycoside nephrotoxicity.
  • To determine if SGLT1 down-regulation contributes to kidney damage caused by aminoglycosides.

Main Methods:

  • In vitro studies using pig proximal tubular LLC-PK(1) cells to assess glucose transport.
  • Analysis of SGLT1 mRNA and protein expression levels in cell cultures.
  • In vivo studies in murine models treated with gentamicin C.
  • Measurement of SGLT1 mRNA expression in kidney tissue.
  • Monitoring urinary glucose excretion in treated mice.

Main Results:

  • Aminoglycosides significantly inhibited Na+/glucose cotransporter (SGLT1)-dependent glucose transport in vitro.
  • Both mRNA and protein levels of SGLT1 were down-regulated by aminoglycosides in LLC-PK(1) cells.
  • Gentamicin C treatment led to down-regulation of SGLT1 mRNA in murine kidneys.
  • Mice treated with gentamicin C exhibited increased urinary glucose excretion.

Conclusions:

  • Down-regulation of SGLT1 is a significant mechanism contributing to aminoglycoside nephrotoxicity.
  • Impaired glucose reabsorption due to reduced SGLT1 function plays a role in kidney damage.
  • These findings provide novel insights into the molecular basis of aminoglycoside-induced kidney injury.

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