Direct and indirect mechanisms of GLP-1 action
Description: Glucagon-like peptide-1 is a naturally occurring gut hormone that controls blood sugar, appetite, and body weight. These actions have supported development of multiple GLP-1-based drugs for the treatment of people with type 2 diabetes and obesity. The actions of GLP-1 are mediated through a single receptor protein, the GLP-1 receptor (GLP-1R). To date, these actions are only partially understood. Development of new GLP-1-based medicines with improved efficacy and safety requires a detailed understanding of how and where the key actions of GLP-1 occur. The proposed studies will study how GLP-1 reduces inflammation, and improves the health of blood vessels, the liver, and kidney, organs involved in the complications of type 2 diabetes and obesity. The experiments will utilize pharmacology and mouse genetics to activate or reduce GLP-1R signaling in different organs and cell types, in mouse models with experimental inflammation, or experimental diabetes, kidney disease, liver disease and obesity. Collectively, we expect the results of these experiments to greatly enhance our detailed understanding of how and where GLP-1 works, enabling greater knowledge of whether and how GLP-1-based medicines may be effectively used to treat the complications of type 2 diabetes and obesity. As GLP-1-based medicines are being tested in people with heart disease, liver disease, kidney disease, and neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, a detailed understanding of how GLP-1 works will enhance the safety and likelihood of success of emerging GLP-1 therapies.
Amount: CA$998,300
Funding type: research
Funder scheme: Project Grant
Start date: 2024-07-01
End date: 2029-06-30
Investigator: Daniel Drucker
Institution: Lunenfeld-Tanenbaum Research Institute (Toronto)
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 192044_1
OpenAlex ID: G5633679686