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Mol Biol Rep. 2013 Mar;40(3):2273-9. doi: 10.1007/s11033-012-2290-8. Epub 2012 Nov 28.

GLP-1-dependent and independent effects and molecular mechanisms of a dipeptidyl peptidase 4 inhibitor in vascular endothelial cells.

Author information

Eastern Clinical Research Unit, Translational Research Division, Department of Medicine, Australian Centre for Blood Diseases, Monash University, 89 Commercial Rd., Prahran 3181, Melbourne, VIC, Australia.

Erratum in

  • Mol Biol Rep. 2013 Feb;40(2):2059. Y, Hu [corrected to Hu, Yunshan]; Hb, Liu [corrected to Liu, HongBin]; Rw, Simpson [corrected to Simpson, Richard W]; Ae, Dear [corrected to Dear, Anthony E].


The potential atheroprotective effects of glucagon-like peptide-1 (GLP-1), long-acting GLP-1 analogues and inhibitors of the enzyme dipeptidyl peptidase 4 (DPP-4) are currently the subject of intense research. Recent evidence suggests the effects of DPP-IV inhibitors, may, in-part, be mediated by GLP-1 independent molecular mechanisms. In this report we demonstrate that treatment of human vascular endothelial cells with the DPP-IV inhibitor sitagliptin inhibited tumour necrosis factor alpha (TNFα) induction of plasminogen activator inhibitor type-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein expression and that this effect was observed to be both GLP-1-dependent and independent. Importantly we identify a molecular mechanism involving sitagliptin-mediated attenuation of TNFα-mediated induction of NFκB and orphan nuclear receptor NUR77 mRNA expression, also able to be reproduced, in part, independent of GLP-1. Taken together these observations may serve to provide a molecular explanation, involving transcriptional regulation of gene expression, for recent in vivo studies suggesting DPP-IV inhibitors may have novel, GLP-1 independent, effects in acting to attenuate endothelial cell dysfunction and atherogenesis.

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