TY - JOUR
T1 - Recent advances in understanding GLP-1R (glucagon-like peptide-1 receptor) function
AU - Koole, Cassandra
AU - Pabreja, Kavita
AU - Savage, Emilia E.
AU - Wootten, Denise
AU - Furness, Sebastian G.B.
AU - Miller, Laurence J.
AU - Christopoulos, Arthur
AU - Sexton, Patrick M.
PY - 2013/2
Y1 - 2013/2
N2 - Type 2 diabetes is a major global health problem and there is ongoing research for new treatments to manage the disease. The GLP-1R (glucagon-like peptide-1 receptor) controls the physiological response to the incretin peptide, GLP-1, and is currently a major target for the development of therapeutics owing to the broad range of potential beneficial effects in Type 2 diabetes. These include promotion of glucose-dependent insulin secretion, increased insulin biosynthesis, preservation of β-cell mass, improved peripheral insulin sensitivity and promotion of weight loss. Despite this, our understanding of GLP-1R function is still limited, with the desired spectrum of GLP-1R-mediated signalling yet to be determined. We review the current understanding of GLP-1R function, in particular, highlighting recent contributions in the field on allosteric modulation, probe-dependence and ligand-directed signal bias and how these behaviours may influence future drug development.
AB - Type 2 diabetes is a major global health problem and there is ongoing research for new treatments to manage the disease. The GLP-1R (glucagon-like peptide-1 receptor) controls the physiological response to the incretin peptide, GLP-1, and is currently a major target for the development of therapeutics owing to the broad range of potential beneficial effects in Type 2 diabetes. These include promotion of glucose-dependent insulin secretion, increased insulin biosynthesis, preservation of β-cell mass, improved peripheral insulin sensitivity and promotion of weight loss. Despite this, our understanding of GLP-1R function is still limited, with the desired spectrum of GLP-1R-mediated signalling yet to be determined. We review the current understanding of GLP-1R function, in particular, highlighting recent contributions in the field on allosteric modulation, probe-dependence and ligand-directed signal bias and how these behaviours may influence future drug development.
KW - Allosteric modulation
KW - Biased signalling
KW - G-protein-coupled receptor
KW - Glucagon-like peptide-1
KW - Glucagon-like peptide-1 receptor
KW - Probe-dependence
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U2 - 10.1042/BST20120236
DO - 10.1042/BST20120236
M3 - Article
C2 - 23356279
AN - SCOPUS:84873193828
SN - 0300-5127
VL - 41
SP - 172
EP - 179
JO - Biochemical Society Transactions
JF - Biochemical Society Transactions
IS - 1
ER -