期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 325, 期 1-2, 页码 26-35出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2010.04.022
关键词
Glucagon-like peptide-1 (GLP-1); Exendin-4; Proliferation; Endothelial cell; GLP-1 receptor
资金
- Stiftelsen Olle Engkvist Byggmastare
- Juvenile Diabetes Research Foundation International
- Swedish Society for Medical Research
- Ake Wiberg's foundation
- EFSD/GSK
- Merck Sharp Dohme
Endothelial cells have a robust capacity to proliferate and participate in angiogenesis, which underlies the maintenance of intimal layer integrity. We previously showed the presence of the GLP-1 receptor in human coronary artery endothelial cells (HCAECs) and the ameliorative actions of GLP-1 on endothelial dysfunction in type 2 diabetic patients. Here, we have studied the effect of exendin-4 on cell proliferation and its underlying mechanisms in HCAECs. Incubation of HCAECs with exendin-4 resulted in a dose-dependent increase in DNA synthesis and an increased cell number, associated with an enhanced eNOS and Akt activation, which were inhibited by PKA, PI3K, Akt or eNOS inhibitors and abolished by a GLP-1 receptor antagonist. Similar effects were obtained by applying GLP-1 (7-36) or GLP-1 (9-36). Co-incubation of exendin-4 and GLP-1 did not show additive effects. Our results suggest that exendin-4 stimulates proliferation of HCAECs through PKA-PI3K/Akt-eNOS activation pathways via a GLP-1 receptor-dependent mechanism. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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