Supported Research

Lay Abstract

We have worked with several diabetic models (8-10, 12) and have the materials and technical expertise to carry out the proposed biochemical, functional, and translational studies at the Kidney Research Centre. Considering the timeline needed to conduct these long-term studies, we expect to complete Aims 1 and 2 in the first 2 years. The diabetic mouse is an ideal model for completing these studies, since pre-clinical data would provide mechanistic insight. Since SGLT2 inhibitors are promising anti-hyperglycemic agents with beneficial cardiovascular and renal outcomes, our work is essential to determine the consequences of prolonged therapy to tubule integrity and function and can be directly translated to human diabetes. Prolonged SGLT2 inhibition will disrupt renal transport, and our work will clarify the underlying mechanisms leading to compensation by the nephron or excessive loss of sodium and water. The completion of this work should confirm that prolonged use of SGLT2 inhibitors leads to distal nephron overload and potential transport dysfunction. Our laboratory is the only one in Canada capable of routinely doing microperfused PT, TAL and CD in vitro allowing us to dissect the effects of SGLT2 inhibitors on transport function and assess the role of PGE /EP and also to target specific EP receptors to prevent distal nephron overload associated with Empa inhibition. The diabetic mouse is an ideal model to delineate the effects of long-term renal exposition of Empa in DKD.