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Glucagon-like peptide-1 (GLP-1) and ...

Krasner, Nadia Marie.

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Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms./
作者:	Krasner, Nadia Marie.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2014,
面頁冊數:	168 p.
附註:	Source: Dissertation Abstracts International, Volume: 75-10(E), Section: B.
Contained By:	Dissertation Abstracts International75-10B(E).
標題:	Medicine. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3627482
ISBN:	9781321027716

Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms.
Krasner, Nadia Marie.

Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms. - Ann Arbor : ProQuest Dissertations & Theses, 2014 - 168 p.

Source: Dissertation Abstracts International, Volume: 75-10(E), Section: B.

Thesis (Ph.D.)--Boston University, 2014.

Glucagon-like peptide-1 (GLP-1) synthetic analog therapies are prescribed for type 2 diabetes due to their effects on insulin and glucagon secretion, and glycemic control. Recent studies also suggest that they may have cardiovascular benefits; however, the mechanism responsible for this is unknown. To examine this question, we evaluated the effects of GLP-1 and the GLP-1 synthetic analog, liraglutide on cell signaling and function in human aortic endothelial cells (HAECs). The results indicate that both agents inhibit TNF&agr; and LPS induced cellular adhesion molecule expression and monocyte adhesion. They also show that incubation with 30pM GLP-1 and 100nM liraglutide stimulates an immediate increase in intracellular calcium, which activates calcium/calmodulin-dependent protein kinase kinase beta (CaMKKbeta). This in turn led to a 2.5 fold increase in the phosphorylation of both AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent protein kinase 1 (CaMK1) within 5 minutes. In addition both GLP-1 and liraglutide caused a 2-fold increase in the phosphorylation of the downstream AMPK/CaMK1 targets: endothelial nitric oxide synthase (eNOS) and cAMP response element-binding protein (CREB). Inhibition of CaMKKbeta with STO-609 (0.5ug/mL) blocked the phosphorylation of both AMPK and CaMK1, confirming its pivotal role. Incubation of the HAECs for three hours with lipopolysaccharide (LPS, 2ug/mL) and TNF&agr; (10ng/mL) increased the expression of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by 5 and 2 fold, respectively. Comparable increases in THP-1 monocyte adhesion to the HAECs, a putative initiating event in atherogenesis, also occurred. Pre-incubation for one hour with either GLP-1 or liraglutide inhibited these events. Likewise, pre-incubation with the CaMKK inhibitor STO-609, or use of lentivirus shRNA to knock down AMPK, blocked the inhibitory effects of both GLP-1 and liraglutide on monocyte adhesion. These results suggest that the recently observed cardiovascular benefits of GLP-1 and liraglutide could be mediated by their effects on CaMKKbeta, AMPK and CaMK1 activation, which lead to decreased adhesion molecule expression and monocyte adhesion in endothelial cells. The finding that these effects occur at concentrations of GLP-1 (30pM) and liraglutide (100nM) observed in vivo also suggests they are physiologically relevant.

ISBN: 9781321027716Subjects--Topical Terms:

641104
Medicine.

Glucagon-like peptide-1 (GLP-1) and liraglutide, a synthetic GLP-1 analog, inhibit inflammation in human aortic endothelial cells via calcium and AMPK dependent mechanisms.
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