Figure 5. Enhancement of central metabolic pathways with SGLT2 inhibition in TAL.

(A) Enrichment analysis using Reactome database of suppressed transcripts with SGLT2 inhibition. (B) Enrichment analysis using Reactome data of enhanced transcripts with SGLT2 inhibition showing metabolism has greatest number of altered transcripts (n > 200). A pathway was considered significant if its P value was less than 0.05 and included at least 5 transcripts reversed by SGLT2i. (C) Bar plots showing transcript-level alterations (log₂FC) when comparing T2Di(–) to HCs (pink) and T2Di(+) to T2Di(–) (blue) (D) Schematic summarizing the transcriptional changes in TAL cells. Increased sodium-chloride delivery to tubular lumen would increase ATP consumption by sodium/potassium ATPase on the basolateral membrane. Increased energy needs could be met by increased expression of glycolytic, TCA cycle, and fatty acid oxidation transcripts.