Digging deep into cells to find mechanisms of kidney protection by SGLT2 inhibitors.
Publication Title
The Journal of clinical investigation
Document Type
Article
Publication Date
3-1-2023
Keywords
washington; spokane; Animals; Mice; Sodium-Glucose Transporter 2 Inhibitors; Sodium-Glucose Transporter 2; Diabetes Mellitus, Type 2; Kidney; Mechanistic Target of Rapamycin Complex 1
Abstract
The sodium-glucose cotransporter-2 (SGLT2) is expressed on the luminal side of proximal tubule epithelial cells in the kidney. While pharmacological inhibition of SGLT2 provides kidney protection in diabetic kidney disease (DKD), the molecular mechanisms remain unclear. In this issue of the JCI, Schaub et al. report on the changes in single-cell transcriptional profiles of young participants with type 2 diabetes who received SGLT2 inhibitors. Treatment with SGLT2 inhibitors restored metabolic perturbations in proximal tubular cells and reduced expression of the inflammatory signaling molecule mTORC1. Notably, changes in transcripts and mTORC1 were also found in the kidney of a diabetes mouse model treated with an SGLT2 inhibitor, supporting use of this model for further studies. These findings reveal cellular mechanisms of SGLT2 inhibitors and are important for advancing therapeutic targets in the treatment of DKD.
Area of Special Interest
Kidney & Diabetes
Specialty/Research Institute
Nephrology
Specialty/Research Institute
Endocrinology
DOI
10.1007/s40271-022-00605-8
