alexa GLP-1 Receptor
ISSN: 2161-0479
Journal of Autacoids and Hormones
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

The Effects of GLP-1 Receptor Agonists on Endothelial Function: Do They Function Directly or Indirectly?

Masataka Kudo1, Akiko Saito-Hakoda2, Ken Matsuda1, Kyoko Shimizu2, Ikuko Sato2, Akira Uruno3, Takeo Yoshikawa4, Yuko Iki2, Kaori Sugawara2, Naotaka Kogure2, Takako Saito-Ito2 , Sadayoshi Ito1 and Akira Sugawara2*
1Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
2Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai, Japan
3Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan
4Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan
Corresponding Author : Akira Sugawara
Department of Molecular Endocrinology
Tohoku University Graduate School of Medicine
Seiryo-machi, Aoba-ku
Sendai, 980-8575 Japan
Tel: +81-22-717-7483
Fax: +81-22-717-8083
E-mail: [email protected]
Received December 27, 2012; Accepted December 28, 2012; Published December 29, 2012
Citation: Kudo M, Saito-Hakoda A, Matsuda K, Shimizu K, Sato I, et al. (2013) The Effects of GLP-1 Receptor Agonists on Endothelial Function: Do They Function Directly or Indirectly? Autacoids 2:e121. doi: 10.4172/2161-0479.1000e121
Copyright: © 2013 Kudo M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Related article at
DownloadPubmed DownloadScholar Google

Visit for more related articles at Journal of Autacoids and Hormones

Glucagon-like peptide 1 (GLP-1) receptor agonists, as well as dipeptidyl peptidase-4 inhibitors, have recently been widely used as therapeutics of type 2 diabetes [1]. According to the accumulation of clinical experience, cardiovascular protective effects of GLP-1 receptor agonists have been focused [2,3]. Although these effects may partly be due to their indirect glucose-lowering and weight-losing effects [4], recent evidence has indicated their direct effects on endothelium.
 
GLP-1 receptor, a seven-transmembrane G-protein coupled receptor consists of 463 amino acids, is not only expressed in pancreatic islets, but also in broad range of organs including endothelium [5]. A GLP-1 receptor agonist liraglutide has been demonstrated to stimulate endothelial nitric oxide (NO) synthase (eNOS) phosphorylation at Ser-1177/NO production via AMP-activated protein kinase (AMPK) activation in human umbilical vein endothelial cells (HUVEC) [6]. Another GLP-1 receptor agonist exenatide also induced eNOS phosphorylation at Ser-1177 in HUVEC, indicating that the effect is mediated via GLP-1 receptor [7]. However, GLP-1(9-36), which has a weak affinity for GLP-1 receptor, also stimulated eNOS phosphorylation at Ser-1177 in HUVEC [7]. Additionally, NO-mediated vasodilatory effects by GLP-1 and GLP-1(9-36) were maintained in Glp-1r-/- mice [8]. Therefore, the existence of GLP-1 receptor-independent pathway for eNOS phosphorylation/NO production is also speculated.
Regarding the signal transduction of GLP-1-mediated eNOS phosphorylation/NO production, involvement of protein kinase A (PKA) has also been demonstrated in bovine aortic EC [9]. Recently, GLP-1 receptor/cyclic AMP/PKA/liver kinase B1 (LKB1)/AMPK/eNOS cascade has been proposed for the GLP-1-stimulated NO production [10]. The phosphoinositide 3-kinase (PI3K)/Akt cascade is also recognized as an important pathway for eNOS phosphorylation [11]. Although exenatide has been shown to induce eNOS phosphorylation at Ser-1177 via both PKA and PI3K/Akt pathways in human coronary artery EC [12], the significance of PI3K/Akt cascade in the GLP-1- mediated NO production remains uncertain. We therefore performed DNA microarray analyses to examine the effect of liraglutide on human coronary artery EC gene expression. Interestingly, we observed that liraglutide significantly up-regulated (3.2-fold) the expression of p87 (PIKAP), which is a novel regulatory subunit of PI3K p110gamma [13] (Kudo et al. unpublished data). Further studies are needed to define the importance of PI3K/Akt pathway and its crosstalk with PKA/LKB1/ AMPK cascade in the GLP-1-mediated eNOS phosphorylation/NO production.
References













Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Article Usage

  • Total views: 11542
  • [From(publication date):
    May-2013 - Aug 22, 2017]
  • Breakdown by view type
  • HTML page views : 7776
  • PDF downloads :3766
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords