Title of project

Analysis of kidney metabolic function in GLP-1 agonism

Abstract

Approximately one out of three adults with diabetes have chronic kidney disease. Dia-betic kidney disease (DKD) is the leading cause of kidney replacement therapy and poses a significant social and economic burden. Glucagon like peptide-1 (GLP-1) is an incretin that lowers glucose levels in the body by increasing insulin release while low-ering glucagon release. Beyond treating diabetes, GLP-1 receptor agonists (GLP1a) are under intensive investigation for their benefits of actions in cardiovascular disease and kidney disease. Along with some glucose-lowering agents such as sodium/glucose co-transporter 2 (SGLT2) inhibitors, GLP-1RAs are suggested to have pleiotropic renal pro-tective effects. However, due to the complex nature of human metabolism, the exact mechanisms of renal effects and protection are still unknown. Here in this project, we aim to investigate kidney metabolism in GLP1a treated patients systematically with in-tegrative omics technologies. We hypothesize integrated proteomics and metabo-lomics profiling will lead us to understand the action of GLP1a on kidney function and discover novel drug targets for add-on therapy of DKD. In this work program, we will collaborate with Novo Nordisk to acquire molecular data of circulating biomolecules from patients treated with GLP1a. We will integrate untargeted metabolomics profil-ing (from patients with Type 2 Diabetes) and targeted proteomics profiling (from hu-man biopsies) and determine the mode of action of circulating biomolecules with highest relevance for kidney disease. In conclusion, we expect to generate a broadly useful atlas that allows identifying potential novel targets for drug development.