Journal article
Glucagon-like peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products–induced inflammation
KC Sourris, Y Ding, SS Maxwell, A Al-sharea, P Kantharidis, M Mohan, CJ Rosado, SA Penfold, C Haase, Y Xu, JM Forbes, S Crawford, G Ramm, BE Harcourt, K Jandeleit-Dahm, A Advani, AJ Murphy, DB Timmermann, A Karihaloo, LB Knudsen Show all
Kidney International | Published : 2024
Open access
Abstract
Glucagon like peptide-1 (GLP-1) is a hormone produced and released by cells of the gastrointestinal tract following meal ingestion. GLP-1 receptor agonists (GLP-1RA) exhibit kidney-protective actions through poorly understood mechanisms. Here we interrogated whether the receptor for advanced glycation end products (RAGE) plays a role in mediating the actions of GLP-1 on inflammation and diabetic kidney disease. Mice with deletion of the GLP-1 receptor displayed an abnormal kidney phenotype that was accelerated by diabetes and improved with co-deletion of RAGE in vivo. Activation of the GLP-1 receptor pathway with liraglutide, an anti-diabetic treatment, downregulated kidney RAGE, reduced the..
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Awarded by Department of Medicine, Georgetown University
Funding Acknowledgements
We thank Dr. Benjamin J. Lamont, Dr. Sih Min Tan, Dr. Gavin C. Higgins, Dr. Matthew Snelson, Dr. Runa Lindblom, Ms. Tuong-Vi Nguyen, Ms. Jenny Wang, Ms. Sarah Rosli, Mrs. Maryann Arnstein, and Dr. Anna Watson for their technical assistance and Dr. Henrik Sondergaard (Novo Nordisk) for his contribution to these studies. We would like to thank Emeritus Professor George Jerums (Austin Health and the University of Melbourne, Department of Medicine) for his input into these studies. We acknowledge the assistance of the Clive and Vera Ramaciotti Centre for Structural Cryo-Electron Microscopy, Monash University, Australia. This work was completed with support from the Diabetes Australia Research Program (Y12V-SOUK) , Novo Nordisk (584803) , and the Victorian Government 's Operational Infrastructure Support Program. KCS has been supported by the Diabetes Australia Research Trust Viertel Postdoctoral Fellowship and a Diabetes Australia Research Program grant. MTC is the recipient of a Career Development Award from JDRF Australia, the recipient of the Australian Research Council Special Research Initiative in Type 1 Juvenile Diabetes. MEC and JMF are recipients of NHMRC Investigator Grants. AE-O is an NHMRC Senior Research Fellow (1154650) . DJD is supported in part by a Banting and Best Diabetes Centre-Novo Nordisk Chair and a Sinai Health-Novo Nordisk Foundation fund in regulatory peptides and CIHR grant 154321. Figures were created with BioRender.com .