Recent advances in understanding GLP-1R (glucagon-like peptide-1 receptor) function.
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.
Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
Cassandra
C
Koole
Kavita
K
Pabreja
Emilia E
EE
Savage
Denise
D
Wootten
Sebastian G B
SG
Furness
Laurence J
LJ
Miller
Arthur
A
Christopoulos
Patrick M
PM
Sexton
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000502:physiology; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D018027:Receptors, Glucagon / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1