The complexity of signalling mediated by the glucagon-like peptide-1 receptor

被引：29
作者：
Fletcher, Madeleine M. [1 ]
Halls, Michelle L. [1 ]
Christopoulos, Arthur [1 ]
Sexton, Patrick M. [1 ]
Wootten, Denise [1 ]
机构：
[1] Monash Univ, Monash Inst Pharmaceut Sci, Melbourne, Vic 3052, Australia
来源：
BIOCHEMICAL SOCIETY TRANSACTIONS | 2016年 / 44卷
基金：
英国医学研究理事会;
关键词：
biased signalling; G protein-coupled receptor; glucagon-like peptide-1 receptor; ligand-directed signalling bias; PANCREATIC BETA-CELLS; AGONIST-INDUCED INTERNALIZATION; STIMULATED INSULIN-SECRETION; PROTEIN-KINASE-A; GLP-1; RECEPTOR; HEALTHY-SUBJECTS; DRUG DISCOVERY; HUMAN ISLETS; CYCLIC-AMP; IN-VIVO;
D O I：
10.1042/BST20150244
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The glucagon-like peptide-1 receptor (GLP-1R) is a class B GPCR that is a major therapeutic target for the treatment of type 2 diabetes. The receptor is activated by the incretin peptide GLP-1 promoting a broad range of physiological effects including glucose-dependent insulin secretion and biosynthesis, improved insulin sensitivity of peripheral tissues, preservation of beta-cell mass and weight loss, all of which are beneficial in the treatment of type 2 diabetes. Despite this, existing knowledge surrounding the underlying signalling mechanisms responsible for the physiological actions downstream of GLP-1R activation is limited. Here, we review the current understanding around GLP-1R-mediated signalling, in particular highlighting recent contributions to the field on biased agonism, the spatial and temporal aspects for the control of signalling and how these concepts may influence future drug development.
引用
收藏
页码：582 / 588
页数：7
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