Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor

Abstract

We aimed to determine the metabolomic profile of kidney cells under high glucose conditions and following sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. Targeted metabolomics using the Absolute IDQ-p180 kit was applied to quantify metabolites in kidney cells stimulated with high glucose (25 and 50 mM) and treated with SGLT2 inhibitor, dapagliflozin (2 µM). Primary cultured human tubular epithelial cells, podocytes, and glomerular endothelial cells were used to identify the metabolomic profile in high glucose conditions following dapagliflozin treatment. The levels of asparagine, PC ae C34:1, and PC ae C36:2 were elevated in tubular epithelial cells stimulated with 50 mM glucose and were significantly decreased after 2 µM dapagliflozin treatment. The level of PC aa C32:0 was significantly decreased after 50 mM glucose treatment compared with the control, and its level was significantly increased after dapagliflozin treatment in podocytes. The level of arginine in glomerular endothelial cells was decreased after stimulation with 50 mM glucose, whereas dapagliflozin treatment significantly elevated its level. The differentially expressed metabolites in kidney cells stimulated by the SGLT2 inhibitor under high glucose conditions were distinct according to cell types.