Glucose/Fructose Delivery to the Distal Nephron Activates the Sodium-Chloride Cotransporter via the Calcium-Sensing Receptor.
Bahena-Lopez JP; Rojas-Vega L; Chavez-Canales M; Bazua-Valenti S; Bautista-Prez R; Lee JH; Madero M; Vazquez-Manjarrez N; Alquisiras-Burgos I; Hernandez-Cruz A; Castaeda-Bueno M; Ellison DH; Gamba G (2023). Glucose/Fructose Delivery to the Distal Nephron Activates the Sodium-Chloride Cotransporter via the Calcium-Sensing Receptor. J Am Soc Nephrol 34 :55-72
The calcium-sensing receptor (CaSR) in the distal convoluted tubule (DCT) activates the NaCl cotransporter (NCC). Glucose acts as a positive allosteric modulator of the CaSR. Under physiologic conditions, no glucose is delivered to the DCT, and fructose delivery depends on consumption. We hypothesized that glucose/fructose delivery to the DCT modulates the CaSR in a positive allosteric way, activating the WNK4-SPAK-NCC pathway and thus increasing salt retention.