Jessica Paola Bahena-Lopez, Lorena Rojas-Vega, María Chávez-Canales, Silvana Bazua-Valenti, Rocío Bautista-Pérez, Ju-Hye Lee, Magdalena Madero, Natalia Vazquez-Manjarrez, Ivan Alquisiras-Burgos, Arturo Hernandez-Cruz, María Castañeda-Bueno, David H Ellison, Gerardo Gamba
BACKGROUND: 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. METHODS: We evaluated the effect of glucose/fructose arrival to the distal nephron on the CaSR-WNK4-SPAK-NCC pathway using HEK-293 cells, C57BL/6 and WNK4-knockout mice, ex vivo perfused kidneys, and healthy humans...
September 7, 2022: Journal of the American Society of Nephrology: JASN