Abstract: SA-PO1172
The SGLT2 Inhibitor Canagliflozin Reverts Hyperglycemia-Induced Metabolic Changes in Mouse Kidney Sections
Session Information
- NIDDK KUH Summer Undergraduate Research Program Posters
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Author
Group or Team Name
- Jose Chevere-Reyes. The University of Texas at San Antonio, San Antonio, TX.
Background
Diabetes is associated with high rates of renal tubular glucose reabsorption, high kidney glycolytic activity and higher production of kidney injury markers. Canagliflozin is an SGLT2 inhibitor, used for type 2 diabetes and considered to have beneficial effects on the progression of diabetic kidney disease. This study tested the effects of Canagliflozin on renal metabolism in mouse kidney slices.
Methods
Kidneys were harvested from C57Bl/6 WT mice, sliced to 150 μM thick sections and incubated in media containing 7.2 mM glucose (NG) or 25 mM glucose (HG), without or with canagliflozin (1, 10 and 100 μM). Conditioned media was collected after 24h of incubation and metabolites were measured using YSI bioanalyzer and gas chromatography-mass spectroscopy. Additionally, kidney injury marker (KIM1) was measured by ELISA. Kidney tissues were frozen, sectioned to 10 μm sections using cryostat for mass spectrometry imaging (MSI) to identify spatial changes in glucose.
Results
In conditioned media, significant reduction in glucose (p<0.0001), and succinate and significant lactate (p<0.001) increase was noted in, HG compared to NG. MSI depicted increase in glucose in tissue sections treated with HG suggesting increased glucose uptake. Canagliflozin reduced the glucose uptake in both NG and HG treated tissue sections (p<0.0001 for HG and p<0.01 for NG groups). Likewise, 100 μM canagliflozin significantly reduced lactate in both glucose conditions. High glucose induced succinate and KIM1 were also reduced by canagliflozin.
Conclusion
Above results support the hypothesis that SGLT2 inhibitors, by blocking glucose uptake, can revert the metabolic changes induced by hyperglycemia and protect against tissue injury.