SGLT-2 inhibitors reduce glucose absorption from peritoneal dialysis solution by suppressing the activity of SGLT-2.
Animals
Benzhydryl Compounds
/ pharmacology
Cells, Cultured
Dialysis Solutions
/ metabolism
Female
Glucose
/ metabolism
Glucosides
/ pharmacology
Humans
Peritoneal Dialysis
/ methods
Peritoneum
/ metabolism
Rats
Rats, Sprague-Dawley
Sodium-Glucose Transporter 2
/ metabolism
Sodium-Glucose Transporter 2 Inhibitors
/ pharmacology
Empagliflozin
Peritoneal dialysis
Peritoneal mesothelial cells
SGLT-2
SGLT-2 inhibitor
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
06
07
2018
revised:
15
10
2018
accepted:
20
10
2018
entrez:
16
12
2018
pubmed:
16
12
2018
medline:
29
3
2019
Statut:
ppublish
Résumé
Sodium glucose cotransporter-2 (SGLT-2) inhibitors have been widely used in the clinic to reduce blood glucose levels by enhancing glucose excretion. However, whether such agents might also reduce glucose absorption via the peritoneal function of human peritoneal mesothelial cells (HPMCs) that also express SGLT-2 is not clear. An acute peritoneal dialysis (PD) model in nonuremic rats was established. Ratios of peritoneal glucose uptake at D4/D0 of Sprague-Dawley rats treated with the SGLT-2 inhibitor, empagliflozin were tested to evaluate the effect of this inhibitor on peritoneal glucose absorption. An in vitro model of HPMCs obtained from peritoneal dialysate effluent in patients undergoing PD was used. HPMCs were exposed to high glucose (60 mM) in the presence and absence of empagliflozin. Glucose uptake and glucose consumption, which were used to estimate the activity of SGLT-2 in HPMCs, were measured by flow cytometry and hexokinase respectively. The expression of SGLT-2 in both peritoneum and HPMCs was also observed by real-time polymerase chain reaction (PCR), western blot, and immunofluorescence staining. Both ratios of peritoneal glucose uptake at D4/D0 and ultrafiltration of rats treated with 3 mg kg An SGLT-2 inhibitor was able to exert a glucose-lowering effect in peritoneum exposed to PD solution by inhibiting the activity of SGLT-2.
Sections du résumé
BACKGROUND
BACKGROUND
Sodium glucose cotransporter-2 (SGLT-2) inhibitors have been widely used in the clinic to reduce blood glucose levels by enhancing glucose excretion. However, whether such agents might also reduce glucose absorption via the peritoneal function of human peritoneal mesothelial cells (HPMCs) that also express SGLT-2 is not clear.
METHODS
METHODS
An acute peritoneal dialysis (PD) model in nonuremic rats was established. Ratios of peritoneal glucose uptake at D4/D0 of Sprague-Dawley rats treated with the SGLT-2 inhibitor, empagliflozin were tested to evaluate the effect of this inhibitor on peritoneal glucose absorption. An in vitro model of HPMCs obtained from peritoneal dialysate effluent in patients undergoing PD was used. HPMCs were exposed to high glucose (60 mM) in the presence and absence of empagliflozin. Glucose uptake and glucose consumption, which were used to estimate the activity of SGLT-2 in HPMCs, were measured by flow cytometry and hexokinase respectively. The expression of SGLT-2 in both peritoneum and HPMCs was also observed by real-time polymerase chain reaction (PCR), western blot, and immunofluorescence staining.
RESULTS
RESULTS
Both ratios of peritoneal glucose uptake at D4/D0 and ultrafiltration of rats treated with 3 mg kg
CONCLUSION
CONCLUSIONS
An SGLT-2 inhibitor was able to exert a glucose-lowering effect in peritoneum exposed to PD solution by inhibiting the activity of SGLT-2.
Identifiants
pubmed: 30551383
pii: S0753-3322(18)34634-1
doi: 10.1016/j.biopha.2018.10.106
pii:
doi:
Substances chimiques
Benzhydryl Compounds
0
Dialysis Solutions
0
Glucosides
0
Slc5a2 protein, rat
0
Sodium-Glucose Transporter 2
0
Sodium-Glucose Transporter 2 Inhibitors
0
empagliflozin
HDC1R2M35U
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1327-1338Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.