In vitro activity: In human umbilical vein endothelial cells, Teneligliptin promoted the antioxidant response, reduced ROS levels and induced Nrf2-target genes messenger ribonucleic acid expression. Teneligliptin improved proliferation rates in HUVECs exposed to high glucose, regulating the expression of cell-cycle inhibitors markers (P21, P53 and P27), and reducing proapoptotic genes (BAX and CASP3), while promoteed BCL2 expression. Teneligliptin ameliorated high glucose-induced endoplasmic reticulum stress. Teneligliptin exihibited antioxidant properties and overcome the metabolic memory effect induced by chronic exposure to high glucose in HUVECs.

Cell Assay: HUVECs are seeded and allowed to attach overnight. Next day cells are exposed to one of three glucose experimental conditions with or without teneligliptin (at 0.1, 1.0 or 3.0 μmol/L) or sitagliptin (at 0.5 μmol/L): continuous normal glucose (NG-5 mmol/L) for 21 days; continuous high glucose (HG-25 mmol/L) for 21 days; and high-metabolic memory (HM-continuous HG for 14 days, followed by NG for the last 7 days). HUVECs are cultured during the 3 weeks changing the media each 48 h and without passaging the cells.