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Dual SGLT1/SGLT2 inhibitor phlorizin reduces glucose transport in experimental peritoneal dialysis

Martus, Giedre LU orcid ; Bergling, Karin LU and Öberg, Carl M. LU (2023) In Peritoneal Dialysis International 43(2). p.145-150
Abstract

Introduction: Glucose absorption during peritoneal dialysis (PD) is commonly assumed to occur via paracellular pathways. We recently showed that SGLT2 inhibition did not reduce glucose absorption in experimental PD, but the potential role of glucose transport into cells is still unclear. Here we sought to elucidate the effects of phlorizin, a non-selective competitive inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), in an experimental rat model of PD. Methods: A 120-min PD dwell was performed in 12 anesthetised Sprague-Dawley rats using 1.5% glucose fluid with a fill volume of 20 mL with (n = 6) or without (n = 6) intraperitoneal phlorizin (50 mg/L). Several parameters for peritoneal water and solute transport were... (More)

Introduction: Glucose absorption during peritoneal dialysis (PD) is commonly assumed to occur via paracellular pathways. We recently showed that SGLT2 inhibition did not reduce glucose absorption in experimental PD, but the potential role of glucose transport into cells is still unclear. Here we sought to elucidate the effects of phlorizin, a non-selective competitive inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), in an experimental rat model of PD. Methods: A 120-min PD dwell was performed in 12 anesthetised Sprague-Dawley rats using 1.5% glucose fluid with a fill volume of 20 mL with (n = 6) or without (n = 6) intraperitoneal phlorizin (50 mg/L). Several parameters for peritoneal water and solute transport were monitored during the treatment. Results: Phlorizin markedly increased the urinary excretion of glucose, lowered plasma glucose and increased plasma creatinine after PD. Median glucose diffusion capacity at 60 min was significantly lower (p < 0.05) being 196 µL/min (IQR 178–213) for phlorizin-treated animals compared to 238 µL/min (IQR 233–268) in controls. Median fractional dialysate glucose concentration at 60 min (D/D0) was significantly higher (p < 0.05) in phlorizin-treated animals being 0.65 (IQR 0.63–0.67) compared to 0.61 (IQR 0.60–0.62) in controls. At 120 min, there was no difference in solute or water transport across the peritoneal membrane. Conclusion: Our findings indicate that a part of glucose absorption during the initial part of the dwell occurs via transport into peritoneal cells.

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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
glucose absorption, phlorizin, SGLT1 inhibition, SGLT2 inhibition
in
Peritoneal Dialysis International
volume
43
issue
2
pages
145 - 150
publisher
Multimed Inc.
external identifiers
  • scopus:85125285433
  • pmid:35188009
ISSN
0896-8608
DOI
10.1177/08968608221080170
language
English
LU publication?
yes
id
1d1daae0-b06f-4e06-8696-5f64e12ef129
date added to LUP
2022-04-19 13:42:31
date last changed
2024-06-30 22:14:37
@article{1d1daae0-b06f-4e06-8696-5f64e12ef129,
  abstract     = {{<p>Introduction: Glucose absorption during peritoneal dialysis (PD) is commonly assumed to occur via paracellular pathways. We recently showed that SGLT2 inhibition did not reduce glucose absorption in experimental PD, but the potential role of glucose transport into cells is still unclear. Here we sought to elucidate the effects of phlorizin, a non-selective competitive inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), in an experimental rat model of PD. Methods: A 120-min PD dwell was performed in 12 anesthetised Sprague-Dawley rats using 1.5% glucose fluid with a fill volume of 20 mL with (n = 6) or without (n = 6) intraperitoneal phlorizin (50 mg/L). Several parameters for peritoneal water and solute transport were monitored during the treatment. Results: Phlorizin markedly increased the urinary excretion of glucose, lowered plasma glucose and increased plasma creatinine after PD. Median glucose diffusion capacity at 60 min was significantly lower (p &lt; 0.05) being 196 µL/min (IQR 178–213) for phlorizin-treated animals compared to 238 µL/min (IQR 233–268) in controls. Median fractional dialysate glucose concentration at 60 min (D/D<sub>0</sub>) was significantly higher (p &lt; 0.05) in phlorizin-treated animals being 0.65 (IQR 0.63–0.67) compared to 0.61 (IQR 0.60–0.62) in controls. At 120 min, there was no difference in solute or water transport across the peritoneal membrane. Conclusion: Our findings indicate that a part of glucose absorption during the initial part of the dwell occurs via transport into peritoneal cells.</p>}},
  author       = {{Martus, Giedre and Bergling, Karin and Öberg, Carl M.}},
  issn         = {{0896-8608}},
  keywords     = {{glucose absorption; phlorizin; SGLT1 inhibition; SGLT2 inhibition}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{145--150}},
  publisher    = {{Multimed Inc.}},
  series       = {{Peritoneal Dialysis International}},
  title        = {{Dual SGLT1/SGLT2 inhibitor phlorizin reduces glucose transport in experimental peritoneal dialysis}},
  url          = {{http://dx.doi.org/10.1177/08968608221080170}},
  doi          = {{10.1177/08968608221080170}},
  volume       = {{43}},
  year         = {{2023}},
}