Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats

by Selleckchem | Sep 10 2023

Background: Harmful glucose exposure and absorption remain major limitations of peritoneal dialysis (PD). We previously showed that inhibition of sodium glucose cotransporter 2 did not affect glucose transport during PD in rats. However, more recently, we found that phlorizin, a dual blocker of sodium glucose cotransporters 1 and 2, reduces glucose diffusion in PD. Therefore, either inhibiting sodium glucose cotransporter 1 or blocking facilitative glucose channels by phlorizin metabolite phloretin would reduce glucose transport in PD.

Methods: We tested a selective blocker of sodium glucose cotransporter 1, mizagliflozin, as well as phloretin, a nonselective blocker of facilitative glucose channels, in an anesthetized Sprague-Dawley rat model of PD.

Results: Intraperitoneal phloretin treatment reduced glucose absorption by >30% and resulted in a >50% higher ultrafiltration rate compared with control animals. Sodium removal and sodium clearances were similarly improved, whereas the amount of ultrafiltration per millimole of sodium removed did not differ. Mizagliflozin did not influence glucose transport or osmotic water transport.

Conclusions: Taken together, our results and previous results indicate that blockers of facilitative glucose channels may be a promising target for reducing glucose absorption and improving ultrafiltration efficiency in PD.

Comments:

The study you described investigates the effects of two different blockers on glucose transport and ultrafiltration in peritoneal dialysis (PD) using a rat model. The aim of the study was to determine if inhibiting sodium glucose cotransporter 1 (SGLT1) or blocking facilitative glucose channels with phloretin could reduce glucose absorption and improve ultrafiltration in PD.

The first blocker tested was mizagliflozin, a selective blocker of SGLT1. However, the results showed that mizagliflozin did not have any significant effect on glucose transport or osmotic water transport during PD.

The second blocker tested was phloretin, a nonselective blocker of facilitative glucose channels. The findings demonstrated that intraperitoneal treatment with phloretin resulted in a reduction of glucose absorption by more than 30% compared to the control group. Additionally, the ultrafiltration rate was more than 50% higher in the phloretin-treated animals. The study also observed improvements in sodium removal and sodium clearances with phloretin treatment. Importantly, the amount of ultrafiltration per millimole of sodium removed did not differ significantly between the control group and the phloretin-treated group.

Based on these results, the authors concluded that blocking facilitative glucose channels, such as with phloretin, may be a promising approach for reducing glucose absorption and improving ultrafiltration efficiency in PD. These findings, in combination with previous research, suggest that inhibitors of facilitative glucose channels could be a potential target for therapeutic interventions to enhance the effectiveness of PD.

It's worth noting that the study was conducted in an anesthetized Sprague-Dawley rat model, and further research is necessary to determine the efficacy and safety of these blockers in human PD patients.