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

Microvasc Res. 2012 Nov;84(3):395-8. doi: 10.1016/j.mvr.2012.06.008. Epub 2012 Jun 30.


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-κB 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-κB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin II Type 1 Receptor Blockers / metabolism
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Diabetic Nephropathies / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic*
  • Glucagon-Like Peptide 1 / physiology*
  • Hormones / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Isoquinolines / pharmacology
  • Mesangial Cells / cytology*
  • NF-kappa B / metabolism
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • RNA, Messenger / metabolism
  • Sulfonamides / pharmacology
  • Up-Regulation


  • Angiotensin II Type 1 Receptor Blockers
  • Enzyme Inhibitors
  • Hormones
  • Isoquinolines
  • NF-kappa B
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Sulfonamides
  • Angiotensin II
  • Intercellular Adhesion Molecule-1
  • Glucagon-Like Peptide 1
  • Cyclic AMP-Dependent Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide