Exendin-4 stimulates proliferation of human coronary artery endothelial cells through eNOS-, PKA- and PI3K/Akt-dependent pathways and requires GLP-1 receptor

被引：195

作者：

Erdogdu, O.

Nathanson, D. ^{[1
]}

Sjoholm, A. ^{[1
]}

Nystrom, T. ^{[1
]}

Zhang, Q. ^{[1
]}

机构：

[1] Karolinska Inst, Dept Clin Sci & Educ, Soder Sjukhuset, Div Internal Med,Unit Diabet Res, Stockholm, Sweden

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2010年 / 325卷 / 1-2期

关键词：

Glucagon-like peptide-1 (GLP-1); Exendin-4; Proliferation; Endothelial cell; GLP-1; receptor; GLUCAGON-LIKE PEPTIDE-1; NITRIC-OXIDE SYNTHASE; DEPENDENT PROTEIN-KINASE; IN-VIVO; PHOSPHATIDYLINOSITOL; 3-KINASE; TRANSCRIPTION FACTOR; BETA-CELLS; PHYSIOLOGICAL FUNCTIONS; MEDIATES ANGIOGENESIS; INSULIN-RESISTANCE;

D O I：

10.1016/j.mce.2010.04.022

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：26 / 35

页数：10

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