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Role of the vascular smooth muscle GLP-1 receptor in renoprotection

Kyle Medak
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
KRESCENT Post-Doctoral Fellowship
2023 - 2026
$165,000
Diabetes

Lay Abstract

Diabetes is associated with the development of complications impacting the heart, blood vessels, eyes, and kidneys. Over time, a substantial number of people with diabetes will exhibit compromised kidney function. The emergence of new glucose-lowering therapies with actions on the kidney has sparked interest in answering the following question. “Can the glucose-lowering therapies based on the hormone GLP-1 also halt the progression of kidney disease in people living with diabetes?” Purpose: I wish to understand the importance of the GLP-1 system in the kidney to ultimately determine whether GLP-1 drugs might slow the progression of diabetes associated kidney disease? Method: I will carry out experiments to activate the GLP-1 system in the mouse kidney, using clinically approved GLP-1 drugs administered to mice with experimental kidney disease. I will also examine the importance of the GLP-1 system in mice by deleting the receptor for GLP-1 in the mouse kidney using genetic techniques. Anticipated Outcomes: I expect that my studies will reveal that the GLP-1 system is essential for kidney health, and our experiments will provide a greater detailed understanding of exactly how GLP-1 improves kidney health, directly and indirectly, in the presence or absence of diabetes. Patient Engagement: Our basic science studies and results are periodically communicated to people living with diabetes and kidney disease through outreach programs established by the Leadership Sinai Diabetes Centre at Mt. Sinai Hospital, as well as through research discussions with the lay public, held every several months, organized by the Mt. Sinai Hospital Foundation. We will also communicate our work, when the opportunity arises, through engagement sessions organized by the Canadian Kidney Foundation, Diabetes Canada and related local and national organizations. Relevance to Patients/Community: People living with diabetes are at risk for developing chronic kidney disease, and existing therapies remain suboptimal. Our studies may highlight new opportunities for using already approved GLP-1-based glucose-lowering medicines to halt the development of diabetes-associated kidney disease. Conclusion The Drucker lab has worked successfully to develop new classes of medicines for the treatment of disease such as diabetes, obesity, and intestinal failure. We are hopeful that the proposed studies will highlight new opportunities to understand how already approved glucose-lowering medicines might favorably interact with and improve kidney health.