Mechanisms of Insulin Receptor-regulated Sodium and Glucose Co-Transport
Diabetes is the leading cause of end-stage kidney disease worldwide. About 40% of people with chronic kidney disease have type 2 diabetes. People with chronic kidney disease have a high risk of heart/vascular events. High blood insulin relates to kidney disease, but what insulin does in the kidney is not well known. Drugs that block a transporter called SGLT2 are FDA approved class of anti-diabetic diuretics that promote glycosuria and reduce the progression of diabetic kidney disease. Our group found that insulin stimulates SGLT2. We think that this may explain the connection between insulin and kidney disease. However, the mechanism is unknown. Based on our experiments, we think that insulin regulates the level of the activated SGLT2. We hypothesize that insulin does this by changing metabolic enzymes. Therefore, we propose to identify the active form(s) of SGLT2. Then, we will study how insulin changes SGLT2 in the context of diabetes and diabetic kidney disease. Our proposal will help us to understand how insulin-regulated SGLT2 affects kidney disease.