Figure 8.

Integrated views on the reconfiguration by SGLT2i of the early proximal tubule and systemic metabolic communication. A, Summary of findings and metabolic communication of SGLT2i (sodium-glucose cotransporter 2 inhibitor) in an early proximal tubule centric view in wild-type (WT) mice. Proteins with red lining were upregulated and proteins with blue lining were downregulated by SGLT2i. Proteins showing green filling have been shown to interact with SGLT2 in affinity purification analysis (see also Figure 2D). For further discussion, see text and Figure S8. B, Summary of findings and metabolic communication of SGLT2i on a systemic level in WT mice. C, Chemical structures of SGLT2 inhibitors dapagliflozin and empagliflozin and p-cresol. ACAT3 indicates acetyl-coenzyme A acetyltransferase 3; AGE, advanced glycation end products; AMPK, 5′-adenosine monophosphate–activated protein kinase; CKD, chronic kidney disease; ER, endoplasmic reticulum; GLUT2, glucose transporter 2; HGD, homogentisate 1,2-dioxygenase; NHE3, Na⁺/H⁺ exchanger 3; OAT1, organic anion transporter 1; PDZK1IP1, PDZK1 interacting protein 1; SLC, solute carrier; TMEM27, transmembrane protein 27; and WAT, white adipose tissue.