495-P: Kidney May Regulate SGLT2-Dependent Glucose Reabsorption through Sweet Taste Receptors: Implications for Diabetes

Abstract

Sodium-glucose cotransporter 2 (SGLT2) mediates 90% glucose reabsorption in kidney, and SGLT2 inhibitors have emerged as a novel oral antihyperglycaemic agents by selectively reducing renal reabsorption of glucose and sodium. Recent research has suggested that sweet taste receptors (STRs) are important participants of diabetes. However, it is unclear whether STRs regulate reabsorption of glucose via SGLT2 in the pathogenesis of diabetes. Therefore, we evaluated the role and mechanism of STRs in reabsorption of glucose via streptozotocin (STZ)-induced diabetes mouse in vivo and in high glucose-induced mouse glomerular mesangial cells (GMCs) and human proximal renal tubular epithelia cells (HK-2) in vitro. Our results showed that the expression of STRs were obviously downregulated while SGLT2 was upregulated under the condition of diabetes in vivo and in vitro. We hypothesized that high glucose-induced downregulation of STRs might modulate reabsorption of glucose. STRs inhibitor lactisole or siRNA-STRs was used as an intervention reagent respectively, distribution of STRs in vivo was detected by PET/CT via intravenous injection of 18F-labeled lactisole, glucose level, renal pathology and SGLT2 expression in vivo and fluorescence labeled glucose uptake rate in vitro were assayed. The effect of high glucose on STRs and SGLT2 expression as well as the glucose absorption were obviously mitigated by lactisole or siRNA-STRs. Overall, this is the first observation of the potential relationship between STRs and SGLT2, suggesting that kidney may regulate SGLT2-depended glucose reabsorption through STRs, which may act as new therapeutic targets of diabetes. Disclosure L. Zhou: None. W. Huang: None. N. Liu: None. X.M. Ma: None. M. Guo: None. Q. Chen: None. C. Gao: None. Y. Xu: None. Funding National Natural Science Foundation of China (81800741)