ECE2015 Guided Posters Diabetes and obesity–Clinical obesity and cardiovascular (8 abstracts)
The dipeptidyl peptidase-IV inhibitor (gemigliptin) inhibits the expression of vascular adhesion molecules and inflammatory cytokines in HUVECs via Akt- and AMPK-dependent mechanisms
Ho Cheol Hong , Hwan-Jin Hwang , Hyun Jung Lee , Min Jung Lee , Ji A Seo , Sin Gon Kim , Nan Hee Kim , Kyung Mook Choi , Dong Seop Choi , Sei Hyun Baik & Hye Jin Yoo
Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University, Seoul, n/a, Republic of Korea.
Recently, dipeptidyl peptidase-IV (DPP-IV) inhibitor, a major anti-hyperglycaemic agent, has received substantial attention as a possible therapeutic target for inflammatory diseases such as atherosclerosis. However, the direct molecular mechanisms through which DPP-IV inhibitor mediates anti-inflammatory effects in vascular endothelial cells have not been clarified. The effects of the DPP-IV inhibitor, gemigliptin, were analysed in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. Using western blotting, we demonstrated that gemigliptin efficiently increased the level of AMP-activated protein kinase (AMPK) and Akt phosphorylation in a dose-dependent manner. The levels of lipopolysaccharide (LPS)-mediated phosphorylated nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) were significantly decreased after gemigliptin treatment. Furthermore, gemigliptin reduced LPS-induced expression of adhesion molecules and inflammatory cytokines such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, tumour necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL1β), and IL6 in HUVECs. In macrophage-like THP-1 cells, gemigliptin effectively inhibited LPS- and LDL-induced foam cell formation. However, these anti-inflammatory and anti-atherosclerotic effects of gemigliptin in HUVECs and THP-1 cells were significantly reduced after treatment with an AMPK or an Akt inhibitor. Our results suggest that gemigliptin efficiently inhibited LPS-induced pro-inflammatory effects in vascular endothelial cells by attenuating NF-κB and JNK signalling via Akt/AMPK-dependent mechanisms. Therefore, the DPP-IV inhibitor, gemigliptin, may directly protect the vascular endothelium against inflammatory diseases such as atherosclerosis.
Disclosure: This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A1005257).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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