Glucagon-like peptide-1 and candesartan additively improve glucolipotoxicity in pancreatic β-cells

Metabolism. 2011 Aug;60(8):1081-9. doi: 10.1016/j.metabol.2010.11.004. Epub 2011 Jan 20.


Glucagon-like peptide-1 (GLP-1) and angiotensin II type 1 receptor blocker reduce β-cell apoptosis in diabetes, but the underlying mechanisms are not fully understood. We examined the combination effects of GLP-1 and candesartan, an angiotensin II type 1 receptor blocker, on glucolipotoxicity-induced β-cell apoptosis; and we explored the possible mechanisms of the antiapoptotic effects. The effects of GLP-1 and/or candesartan on glucolipotoxicity-induced apoptosis and the phosphorylation of insulin receptor substrate-2 (IRS-2), protein kinase B (PKB), and forkhead box O1 (FoxO1) were evaluated by using MIN6 cells and isolated mouse pancreatic islets. Although palmitate significantly enhanced the high-glucose-induced apoptosis in both islets and MIN6 cells, GLP-1 and candesartan significantly inhibited apoptosis; and combination treatment additively prevented apoptosis. Whereas palmitate significantly decreased the phosphorylation of IRS-2, PKB, and FoxO1 in MIN6 cells, these changes were significantly inhibited by treatment with GLP-1 and/or candesartan. In addition, wortmannin, an inhibitor of phosphoinositide 3-kinase, markedly inhibited GLP-1- and/or candesartan-mediated PKB and FoxO1 phosphorylation. The present results suggest that GLP-1 and candesartan additively prevent glucolipotoxicity-induced apoptosis in pancreatic β-cells through the IRS-2/phosphoinositide 3-kinase/PKB/FoxO1 signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Benzimidazoles / metabolism
  • Benzimidazoles / pharmacology*
  • Biphenyl Compounds
  • Cell Line
  • Dose-Response Relationship, Drug
  • Female
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucose / metabolism
  • Insulin / metabolism
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Mice
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Tetrazoles / metabolism
  • Tetrazoles / pharmacology*


  • Benzimidazoles
  • Biphenyl Compounds
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs2 protein, mouse
  • Tetrazoles
  • Glucagon-Like Peptide 1
  • Proto-Oncogene Proteins c-akt
  • Glucose
  • candesartan