Decreased glucagon-like peptide 1 receptor expression in endothelial and smooth muscle cells in diabetic db/db mice: TCF7L2 is a possible regulator of the vascular glucagon-like peptide 1 receptor

Abstract

Aims: Incretin signalling is known to prevent the development of arteriosclerosis by relaxation response in endothelial cells via the glucagon-like peptide 1 receptor. It remains unclear, however, whether vascular glucagon-like peptide 1 receptor expression is altered under some conditions. The aim of this study is to examine whether vascular glucagon-like peptide 1 receptor expression is altered by diabetic state as reported in pancreatic β-cells. Methods: We used 18-week-old male diabetic db/db mice and control db/m mice. Excised thoracic artery was specifically collected, and vascular endothelial cells were cultured. We compared the glucagon-like peptide 1 receptor expression levels between the db/db and db/m mice. Results: Metabolic parameters were significantly worse in db/db mice. The glucagon-like peptide 1 receptor and transcription factor 7-like 2 expression levels in endothelial and smooth muscle cells were significantly lower in db/db mice. Furthermore, siRNA to transcription factor 7-like 2 decreased the transcription factor 7-like 2 levels and such reduction of the transcription factor 7-like 2 resulted in the downregulation of the glucagon-like peptide 1 receptor expressions in cultured vascular endothelial cells. Conclusion: The glucagon-like peptide 1 receptor expression level was significantly lower under diabetic condition which was accompanied by the reduction of the transcription factor 7-like 2 expression level. Furthermore, the transcription factor 7-like 2 is a possible regulator of the glucagon-like peptide 1 receptor expression in artery as reported in β-cells.