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Transcellular transport of 18F-deoxyglucose via facilitative glucose channels in experimental peritoneal dialysis

Martus, Giedre LU orcid ; Siddhuraj, Premkumar LU ; Erjefält, Jonas S. LU ; Kádár, András LU ; Lindström, Martin LU ; Bergling, Karin LU and Öberg, Carl M. LU (2024) In Peritoneal Dialysis International
Abstract

Background: Local and systemic side effects of glucose remain major limitations of peritoneal dialysis (PD). Glucose transport during PD is thought to occur via inter-endothelial pathways, but recent results show that phloretin, a general blocker of facilitative glucose channels (glucose transporters [GLUTs]), markedly reduced glucose diffusion capacity indicating that some glucose may be transferred via facilitative glucose channels (GLUTs). Whether such transport mainly occurs into (absorption), or across (trans-cellular) peritoneal cells is as yet unresolved. Methods: Here we sought to elucidate whether diffusion of radiolabeled 18F-deoxyglucose ([18F]-DG) in the opposite direction (plasma → dialysate) is also... (More)

Background: Local and systemic side effects of glucose remain major limitations of peritoneal dialysis (PD). Glucose transport during PD is thought to occur via inter-endothelial pathways, but recent results show that phloretin, a general blocker of facilitative glucose channels (glucose transporters [GLUTs]), markedly reduced glucose diffusion capacity indicating that some glucose may be transferred via facilitative glucose channels (GLUTs). Whether such transport mainly occurs into (absorption), or across (trans-cellular) peritoneal cells is as yet unresolved. Methods: Here we sought to elucidate whether diffusion of radiolabeled 18F-deoxyglucose ([18F]-DG) in the opposite direction (plasma → dialysate) is also affected by GLUT inhibition. During GLUT inhibition, such transport may either be increased or unaltered (favors absorption hypothesis) or decreased (favors transcellular hypothesis). Effects on the transport of solutes other than [18F]-DG (or glucose) during GLUT inhibition indicate effects on paracellular transport (between cells) rather than via GLUTs. Results: GLUT inhibition using phloretin markedly reduced [18F]-DG diffusion capacity, improved ultrafiltration (UF) rates and enhanced the sodium dip. No other solutes were significantly affected with the exception of urea and bicarbonate. Conclusion: The present results indicate that part of glucose is transported via the transcellular route across cells in the peritoneal membrane. Regardless of the channel(s) involved, inhibitors of facilitative GLUTs may be promising agents to improve UF efficacy in patients treated with PD.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
BAY-876, GLUT1, indinavir, Peritoneal dialysis, phloretin, ritonavir, ultrafiltration efficiency, [F]-deoxyglucose
in
Peritoneal Dialysis International
publisher
Multimed Inc.
external identifiers
  • scopus:85210948736
  • pmid:39636030
ISSN
0896-8608
DOI
10.1177/08968608241299928
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2024.
id
84221be8-9bab-47df-9b02-40ae70dba078
date added to LUP
2025-01-31 15:52:12
date last changed
2025-07-05 04:39:27
@article{84221be8-9bab-47df-9b02-40ae70dba078,
  abstract     = {{<p>Background: Local and systemic side effects of glucose remain major limitations of peritoneal dialysis (PD). Glucose transport during PD is thought to occur via inter-endothelial pathways, but recent results show that phloretin, a general blocker of facilitative glucose channels (glucose transporters [GLUTs]), markedly reduced glucose diffusion capacity indicating that some glucose may be transferred via facilitative glucose channels (GLUTs). Whether such transport mainly occurs into (absorption), or across (trans-cellular) peritoneal cells is as yet unresolved. Methods: Here we sought to elucidate whether diffusion of radiolabeled <sup>18</sup>F-deoxyglucose ([<sup>18</sup>F]-DG) in the opposite direction (plasma → dialysate) is also affected by GLUT inhibition. During GLUT inhibition, such transport may either be increased or unaltered (favors absorption hypothesis) or decreased (favors transcellular hypothesis). Effects on the transport of solutes other than [<sup>18</sup>F]-DG (or glucose) during GLUT inhibition indicate effects on paracellular transport (between cells) rather than via GLUTs. Results: GLUT inhibition using phloretin markedly reduced [<sup>18</sup>F]-DG diffusion capacity, improved ultrafiltration (UF) rates and enhanced the sodium dip. No other solutes were significantly affected with the exception of urea and bicarbonate. Conclusion: The present results indicate that part of glucose is transported via the transcellular route across cells in the peritoneal membrane. Regardless of the channel(s) involved, inhibitors of facilitative GLUTs may be promising agents to improve UF efficacy in patients treated with PD.</p>}},
  author       = {{Martus, Giedre and Siddhuraj, Premkumar and Erjefält, Jonas S. and Kádár, András and Lindström, Martin and Bergling, Karin and Öberg, Carl M.}},
  issn         = {{0896-8608}},
  keywords     = {{BAY-876; GLUT1; indinavir; Peritoneal dialysis; phloretin; ritonavir; ultrafiltration efficiency; [F]-deoxyglucose}},
  language     = {{eng}},
  publisher    = {{Multimed Inc.}},
  series       = {{Peritoneal Dialysis International}},
  title        = {{Transcellular transport of <sup>18</sup>F-deoxyglucose via facilitative glucose channels in experimental peritoneal dialysis}},
  url          = {{http://dx.doi.org/10.1177/08968608241299928}},
  doi          = {{10.1177/08968608241299928}},
  year         = {{2024}},
}