Glucagon-like peptide-1 inhibits angiotensin II-induced mesangial cell damage via protein kinase A

There is a growing body of evidence that renin-angiotensin system plays a role in diabetic nephropathy. Recently, we have found that glucagon-like peptide-1 (GLP-1), one of the incretins, a gut hormone secreted from L cells in the intestine in response to food intake, inhibits advanced glycation end product-induced monocyte chemoattractant protein-1 gene expression in mesangial cells thorugh the interaction with the receptor of GLP-1. However, effects of GLP-1 on angiotensin II-exposed mesangial cells are unknown. This study investigated whether and how GLP-1 blocked the angiotensin II-induced mesangial cell damage in vitro. GLP-1 completely blocked the angiotensin II-induced superoxide generation, NF-kappa B activation, up-regulation of mRNA levels of intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 in mesangial cells, all of which were prevented by the treatments with H-89, an inhibitor of protein kinase A. The present results demonstrated for the first time that GLP-1 blocked the angiotensin II-induced mesangial cell injury by inhibiting superoxide-mediated NF-kappa B activation via protein kinase C pathway. Our present study suggests that strategies to enhance the biological actions of GLP-1 may be a promising strategy for the treatment of diabetic nephropathy. (C) 2012 Elsevier Inc. All rights reserved.