Top ▲

GLP-1 receptor

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 249

Nomenclature: GLP-1 receptor

Family: Glucagon receptor family

Contents:

Gene and Protein Information Click here for help
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 463 6p21.2 GLP1R glucagon like peptide 1 receptor 34,42
Mouse 7 463 17 15.8 cM Glp1r glucagon-like peptide 1 receptor
Rat 7 463 20p12 Glp1r glucagon-like peptide 1 receptor 19,35
Previous and Unofficial Names Click here for help
GLP-1R | glucagon-like peptide 1 receptor
Database Links Click here for help
Specialist databases
GPCRdb glp1r_human (Hs), glp1r_mouse (Mm), glp1r_rat (Rn)
Other databases
Alphafold P43220 (Hs), O35659 (Mm), P32301 (Rn)
CATH/Gene3D 4.10.1240.10
ChEMBL Target CHEMBL1784 (Hs), CHEMBL1075290 (Mm), CHEMBL5862 (Rn)
DrugBank Target P43220 (Hs)
Ensembl Gene ENSG00000112164 (Hs), ENSMUSG00000024027 (Mm), ENSRNOG00000001152 (Rn)
Entrez Gene 2740 (Hs), 14652 (Mm), 25051 (Rn)
Human Protein Atlas ENSG00000112164 (Hs)
KEGG Gene hsa:2740 (Hs), mmu:14652 (Mm), rno:25051 (Rn)
OMIM 138032 (Hs)
Pharos P43220 (Hs)
RefSeq Nucleotide NM_002062 (Hs), NM_021332 (Mm), NM_012728 (Rn)
RefSeq Protein NP_002053 (Hs), NP_067307 (Mm), NP_036860 (Rn)
SynPHARM 84391 (in complex with Peptide 5 [PMID: 28562585])
84392 (in complex with Peptide 5 [PMID: 28562585])
UniProtKB P43220 (Hs), O35659 (Mm), P32301 (Rn)
Wikipedia GLP1R (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Ligand-bound GLP-1 receptor extracellular domain
PDB Id:  3C5T
Ligand:  glucagon-like peptide 1-(7-36) amide   This ligand is endogenous
Resolution:  2.1Å
Species:  Human
References:  29
Image of receptor 3D structure from RCSB PDB
Description:  Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulator, NNC0640
PDB Id:  5VEX
Ligand:  NNC0640
Resolution:  3.0Å
Species:  None
References:  33
Image of receptor 3D structure from RCSB PDB
Description:  Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulator, PF-06372222
PDB Id:  5VEW
Ligand:  PF-06372222
Resolution:  2.7Å
Species:  None
References:  33
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of the activated Glucagon-like peptide-1 receptor in complex with the stimulatory G protein Gs
PDB Id:  5VAI
Ligand:  glucagon-like peptide 1-(7-36) amide   This ligand is endogenous
Resolution:  4.1Å
Species:  Rabbit
References: 
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the GLP-1 receptor bound to a peptide agonist
PDB Id:  5NX2
Ligand:  Peptide 5 [PMID: 28562585]
Resolution:  3.7Å
Species:  Human
References:  15
Natural/Endogenous Ligands Click here for help
glucagon {Sp: Human, Mouse, Rat}
glucagon-like peptide 1-(7-37) {Sp: Human, Mouse, Rat}
glucagon-like peptide 1-(7-36) amide {Sp: Human, Mouse, Rat}

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
WB4-24 Small molecule or natural product Hs Agonist 4.9 pA2 9
⤷ pA2 4.9 [9]
[125I]GLP-1-(7-36)-amide Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.3 pKd 16
⤷ pKd 9.3 (Kd 5x10-10 M) [16]
glucagon-like peptide 1-(7-36) amide {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist 9.2 pKi 16
⤷ pKi 9.2 [16]
lixisenatide Peptide Approved drug Primary target of this compound Hs Agonist 8.9 pKi 41
⤷ pKi 8.9 (Ki 1.33x10-9 M) [41]
Description: CHO-K1 cells overexpressing the human GLP-1 receptor.
exendin-4 Peptide Approved drug Primary target of this compound Hs Full agonist 8.7 – 9.0 pKi 16
⤷ pKi 8.7 – 9.0 (Ki 1.99x10-9 – 1x10-9 M) [16]
Peptide 5 [PMID: 28562585] Peptide Hs Agonist 8.5 pKi 15
⤷ pKi 8.5 [15]
orforglipron Small molecule or natural product Ligand has a PDB structure Hs Partial agonist 8.5 pKi 17
⤷ pKi 8.5 (Ki 3.22x10-9 M) [17]
Description: Quantified by [125I]GLP-1(7-36) competition binding using GLP-1R expressing cell membranes
tirzepatide Peptide Approved drug Click here for species-specific activity table Hs Agonist 8.4 pKi 5
⤷ pKi 8.4 (Ki 4.23x10-9 M) [5]
glucagon {Sp: Human, Mouse, Rat} Peptide Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.9 – 7.0 pKi 16
⤷ pKi 6.9 – 7.0 [16]
danuglipron Small molecule or natural product Ligand has a PDB structure Hs Agonist 6.4 pKi 11
⤷ pKi 6.4 (Ki 3.6x10-7 M) [11]
Description: Binding affinity of danuglipron evaluated in a competition binding assay with radiolabeled GLP-1 as tracer
semaglutide Peptide Approved drug Primary target of this compound Hs Agonist 11.2 pEC50 21
⤷ pEC50 11.2 (EC50 6.2x10-12 M) [21]
Description: In vitro potency assessed in BHK cells expressing the human GLP-1R and a luciferase reporter system.
Peptide 5 [PMID: 28562585] Peptide Hs Agonist 10.8 pEC50 15
⤷ pEC50 10.8 [15]
taspoglutide Peptide Hs Agonist 10.2 pEC50 30
⤷ pEC50 10.2 (EC50 6x10-11 M) [30]
Description: stimulating cAMP production
liraglutide Peptide Approved drug Primary target of this compound Hs Full agonist 10.2 pEC50 18
⤷ pEC50 10.2 [18]
survodutide Peptide Click here for species-specific activity table Hs Agonist 9.5 pEC50 44
⤷ pEC50 9.5 (EC50 3.3x10-10 M) [44]
Description: Determined using a cAMP assay in CHO-K1 cells expressing hGLPIR
survodutide Peptide Mm Agonist 9.4 pEC50 44
⤷ pEC50 9.4 (EC50 3.6x10-10 M) [44]
Description: Dtermined using a cAMP assay in mouse MIN6 insulinoma cells
maridebart cafraglutide Peptide Click here for species-specific activity table Rn Agonist 8.6 pEC50 39
⤷ pEC50 8.6 (EC50 2.4x10-9 M) [39]
Description: In vitro potency in GLP-1R recombinant cells
maridebart cafraglutide Peptide Click here for species-specific activity table Monkey Agonist 8.2 pEC50 39
⤷ pEC50 8.2 (EC50 5.7x10-9 M) [39]
Description: In vitro potency in GLP-1R recombinant cells
albiglutide Peptide Approved drug Rn Agonist 7.7 pEC50 1
⤷ pEC50 7.7 (EC50 2x10-8 M) [1]
maridebart cafraglutide Peptide Click here for species-specific activity table Hs Agonist 7.6 pEC50 39
⤷ pEC50 7.6 (EC50 2.44x10-8 M) [39]
Description: In vitro potency in GLP-1R recombinant cells
semaglutide Peptide Approved drug Primary target of this compound Hs Agonist 9.4 pIC50 21
⤷ pIC50 9.4 (IC50 3.8x10-10 M) [21]
Description: Membrane radioligand displacement assay (125I-GLP-1 as tracer) performed in the absence of human serum albumin.
exendin-4 Peptide Approved drug Primary target of this compound Hs Agonist 9.2 pIC50 24
⤷ pIC50 9.2 (IC50 6.6x10-10 M) [24]
Description: Displacement of GLP-1 from hGLP-1 receptor expressed in CHOK1 cells by exendin-4
glucagon-like peptide 1-(7-37) {Sp: Human, Mouse, Rat} Peptide Ligand is endogenous in the given species Hs Full agonist - - 6
⤷ [6]
exendin-3 Peptide Hs Full agonist - - 28
⤷ [28]
[125I]GLP-1-(7-37) (human) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist - -
⤷
View species-specific agonist tables
Agonist Comments
The affinities for exendin-4 and its synthetic analogue exenatide are assumed to be interchangeable.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]exendin-(9-39) Peptide Ligand is labelled Ligand is radioactive Hs Antagonist 8.3 pKd 16
⤷ pKd 8.3 (Kd 5x10-9 M) [16]
exendin-(9-39) Peptide Hs Antagonist 8.1 pKi 16
⤷ pKi 8.1 (Ki 7.94x10-9 M) [16]
GLP-1-(9-36) Peptide Rn Antagonist 6.9 pIC50 25
⤷ pIC50 6.9 (IC50 1.224x10-7 M) [25]
T-0632 Small molecule or natural product Hs Antagonist 4.7 pIC50 36
⤷ pIC50 4.7 (IC50 2.1x10-5 M) [36]
View species-specific antagonist tables
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BETP Small molecule or natural product Hs Positive 9.9 pEC50 26
⤷ pEC50 9.9 [26]
LSN3318839 Small molecule or natural product Hs Positive 7.8 pEC50 43
⤷ pEC50 7.8 (EC50 1.4x10-8 M) [43]
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
References:  32
Tissue Distribution Click here for help
Pancreas, lung, brain, stomach, heart and kidney.
None found in liver, skeletal muscle or adipose.
Species:  Human
Technique:  RNase protection assay.
References:  40
Endocrine cells of the pancreas.
Large nucleated cells in the alveoli of the lung, thought to be surfactant-secreting type II pneumocytes.
Gastric pits of the stomach, thought to be parietal cells.
Crypts of the duodenum.
None in the liver, skeletal muscle or adipocytes.
Species:  Rat
Technique:  in situ hybridisation.
References:  4
Stomach: Gastric mucosal glands.
Species:  Rat
Technique:  Radioligand binding.
References:  38
Low levels in the hypothalamus and hindbrain.
Higher expression in the area postrema and arcuate nucleus.
None detected in the cortex.
Species:  Rat
Technique:  RT-PCR.
References:  22
Lung, pancreatic islets, antrum and pylorus of the stomach, and kidney.
Species:  Rat
Technique:  RNase protection assay.
References:  4
Hypothalamus, lung, pancreatic islets, stomach, heart, and kidney.
None found in adipocytes, liver or skeletal muscle.
Species:  Rat
Technique:  RT-PCR and Southern blotting.
References:  4
Hypothalamus: Densest expression on the paraventricular, arcuate and supraoptic nuclei. Scatterered expression in the periventricular and dorsomedial nuclei and the lateral hypothalamus.
Species:  Rat
Technique:  in situ hybridisation.
References:  31
Expression Datasets Click here for help

Show »

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays Click here for help
Measurement of cAMP accumulation in rat insuloma-derived cells (RINm5F).
Species:  Rat
Tissue:  RINm5F cells.
Response measured:  Increase in cAMP production.
References:  14
Measurement of insulin secretion in isolated rat pancreatic islets.
Species:  Rat
Tissue:  Pancreatic islets.
Response measured:  Potentiation of glucose-induced insulin release.
References:  14
Measurement of cAMP levels in HEK 293 cells transfected with the human GLP-1 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  12
Measurement of intracellular [Ca2+] in HEK 293 cells transfected with the human GLP-1 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Mobilisation of Ca2+ from ryanodine-sensitive intracellular stores.
References:  12
Measurement of cAMP levels in the rat gastric gland.
Species:  Rat
Tissue:  Gastric mucosal gland.
Response measured:  Stimulation of cAMP production.
References:  38
Measurement of cAMP levels in cultured rat insulinoma cells.
Species:  Rat
Tissue:  Cultured insulinoma cells.
Response measured:  Stimulation of cAMP accumulation.
References:  7
Measurement of insulin mRNA levels and insulin release in cultured rat insulinoma cells.
Species:  Rat
Tissue:  Cultured insulinoma cells.
Response measured:  Increase in insulin mRNA levels and insulin release.
References:  7
Measurement of the activity of the rat insulin 1 gene promotor (RIP1) cAMP response element (CRE).
Species:  Rat
Tissue:  INS-1 insulinoma cells expressing a RIP1 luciferase construct (-410RIP1-LUC).
Response measured:  Activation of the RIP1 CRE.
References:  32
Measurements of proinsulin gene promotor activity, cellular levels of proinsulin mRNA and insulin content in βTC-1 cells transfected with a rat insulin I gene promotor fused to the transcriptional reporter gene encoding the bacterial enzyme chloramphenicol-acetyltransferase (CAT).
Species:  Mouse
Tissue:  βTC-1 cells (mouse insulinoma cell line) transfected with a rat insulin I gene promotor encoding the bacterial enzyme CAT.
Response measured:  Stimulation of proinsulin gene promotor activity, increases in proinsulin mRNA levels and insulin content.
References:  10
Physiological Functions Click here for help
Relaxation of rat conduit arteries, independent of nitric oxide and the endothelium.
Species:  Rat
Tissue:  Femoral artery rings.
References:  27
Stimulation of pancreatic insulin release.
Species:  Rat
Tissue:  Pancreas.
References:  37
GLP-1 stimulates basal TSH release from thyrotropes and α-TSH cells.
Species:  Rat
Tissue:  Thyrotropes.
References:  2
Stimulation of the central CRH-containing neurons of the hypothalamo-pituitary-adrenocortical axis and oxytocinergic neurons of the hypothalamo-neurohypophysial tract.
Species:  Rat
Tissue:  In vivo
References:  20
Physiological Consequences of Altering Gene Expression Click here for help
GLP-1 receptor knockout mice exhibit a reduced heart rate and elevated left ventricular end diastolic pressure compared to wild-type mice.
They had increased left ventricular thickness and impaired contractility.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  13
GLP-1 receptor knockout mice appear to have normal circulating levels of corticosterone, thyroid hormone, testosterone, estradiol and progesterone. However, they have an impaired stress response, with increased amounts of corticosterone produced in response to stress.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  23
GLP-1 receptor knockout mice show exhibit a learning deficit as well as enhanced seizure severity and neuronal injury following kainate administration.
Species:  Mouse
Tissue: 
Technique: 
References:  8
Rats overexpressing the GLP-1 receptor exhibit improved learning and memory.
Species:  Rat
Tissue: 
Technique: 
References:  8
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Glp1rtm1Ddr Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129/Sv * C57BL/6		 MGI:99571  MP:0002694 abnormal pancreas secretion PMID: 14966573 
Giprtm1Thor|Glp1rtm1Ddr Giprtm1Thor/Giprtm1Thor,Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129/Sv * 129P2/OlaHsd * C57BL/6		 MGI:1352753  MGI:99571  MP:0002694 abnormal pancreas secretion PMID: 14966573 
Glp1rtm1Ddr Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129S1/Sv * 129X1/SvJ		 MGI:99571  MP:0002727 decreased circulating insulin level PMID: 8898756 
Glp1rtm1Ddr Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129/Sv * C57BL/6		 MGI:99571  MP:0002727 decreased circulating insulin level PMID: 14966573 
Giprtm1Thor|Glp1rtm1Ddr Giprtm1Thor/Giprtm1Thor,Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129/Sv * 129P2/OlaHsd * C57BL/6		 MGI:1352753  MGI:99571  MP:0002727 decreased circulating insulin level PMID: 14966573 
Glp1rtm1Ddr Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129S1/Sv * 129X1/SvJ		 MGI:99571  MP:0005293 impaired glucose tolerance PMID: 8898756 
Glp1rtm1Ddr Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129/Sv * C57BL/6		 MGI:99571  MP:0005293 impaired glucose tolerance PMID: 14966573 
Giprtm1Thor|Glp1rtm1Ddr Giprtm1Thor/Giprtm1Thor,Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129/Sv * 129P2/OlaHsd * C57BL/6		 MGI:1352753  MGI:99571  MP:0005293 impaired glucose tolerance PMID: 14966573 
Glp1rtm1Ddr Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129S1/Sv * 129X1/SvJ		 MGI:99571  MP:0005559 increased circulating glucose level PMID: 8898756 
Glp1rtm1Ddr Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129/Sv * C57BL/6		 MGI:99571  MP:0005559 increased circulating glucose level PMID: 14966573 
Giprtm1Thor|Glp1rtm1Ddr Giprtm1Thor/Giprtm1Thor,Glp1rtm1Ddr/Glp1rtm1Ddr
involves: 129/Sv * 129P2/OlaHsd * C57BL/6		 MGI:1352753  MGI:99571  MP:0005559 increased circulating glucose level PMID: 14966573 
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A Thr149->Met substitution within transmembrane 1 of the GLP-1 receptor has been found within a type 2 diabetes patient.
Transfection of the recombinant receptor variant within COS-7 and HEK 293 cells has shown reduced agonist binding and reduced potency in triggering cAMP-mediated signalling.
Amino acid change:  T149M
References:  3
General Comments
Several GLP-1 receptor agonists have now been approved for clinical use to treat type 2 diabetes mellitus, including exenatide, liraglutide, albiglutide and lixisenatide.

References

Show »

1. Baggio LL, Huang Q, Brown TJ, Drucker DJ. (2004) A recombinant human glucagon-like peptide (GLP)-1-albumin protein (albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes, 53 (9): 2492-500. [PMID:15331566]

2. Beak SA, Small CJ, Ilovaiskaia I, Hurley JD, Ghatei MA, Bloom SR, Smith DM. (1996) Glucagon-like peptide-1 (GLP-1) releases thyrotropin (TSH): characterization of binding sites for GLP-1 on alpha-TSH cells. Endocrinology, 137 (10): 4130-8. [PMID:8828468]

3. Beinborn M, Worrall CI, McBride EW, Kopin AS. (2005) A human glucagon-like peptide-1 receptor polymorphism results in reduced agonist responsiveness. Regul Pept, 130 (1-2): 1-6. [PMID:15975668]

4. Bullock BP, Heller RS, Habener JF. (1996) Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology, 137 (7): 2968-78. [PMID:8770921]

5. Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC et al.. (2018) LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab, 18: 3-14. [PMID:30473097]

6. Dillon JS, Tanizawa Y, Wheeler MB, Leng XH, Ligon BB, Rabin DU, Yoo-Warren H, Permutt MA, Boyd AE. (1993) Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor. Endocrinology, 133 (4): 1907-10. [PMID:8404634]

7. Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF. (1987) Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA, 84 (10): 3434-8. [PMID:3033647]

8. During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ et al.. (2003) Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med, 9 (9): 1173-9. [PMID:12925848]

9. Fan H, Gong N, Li TF, Ma AN, Wu XY, Wang MW, Wang YX. (2015) The non-peptide GLP-1 receptor agonist WB4-24 blocks inflammatory nociception by stimulating β-endorphin release from spinal microglia. Br J Pharmacol, 172 (1): 64-79. [PMID:25176008]

10. Fehmann HC, Habener JF. (1992) Insulinotropic hormone glucagon-like peptide-I(7-37) stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma beta TC-1 cells. Endocrinology, 130 (1): 159-66. [PMID:1309325]

11. Griffith DA, Edmonds DJ, Fortin JP, Kalgutkar AS, Kuzmiski JB, Loria PM, Saxena AR, Bagley SW, Buckeridge C, Curto JM et al.. (2022) A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor. J Med Chem, 65 (12): 8208-8226. [PMID:35647711]

12. Gromada J, Rorsman P, Dissing S, Wulff BS. (1995) Stimulation of cloned human glucagon-like peptide 1 receptor expressed in HEK 293 cells induces cAMP-dependent activation of calcium-induced calcium release. FEBS Lett, 373 (2): 182-6. [PMID:7589461]

13. Gros R, You X, Baggio LL, Kabir MG, Sadi AM, Mungrue IN, Parker TG, Huang Q, Drucker DJ, Husain M. (2003) Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology, 144 (6): 2242-52. [PMID:12746281]

14. Göke R, Fehmann HC, Linn T, Schmidt H, Krause M, Eng J, Göke B. (1993) Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. J Biol Chem, 268 (26): 19650-5. [PMID:8396143]

15. Jazayeri A, Rappas M, Brown AJH, Kean J, Errey JC, Robertson NJ, Fiez-Vandal C, Andrews SP, Congreve M, Bortolato A et al.. (2017) Crystal structure of the GLP-1 receptor bound to a peptide agonist. Nature, 546 (7657): 254-258. [PMID:28562585]

16. Jorgensen R, Martini L, Schwartz TW, Elling CE. (2005) Characterization of glucagon-like peptide-1 receptor beta-arrestin 2 interaction: a high-affinity receptor phenotype. Mol Endocrinol, 19 (3): 812-23. [PMID:15528268]

17. Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA et al.. (2020) Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Proc Natl Acad Sci U S A, 117 (47): 29959-29967. [PMID:33177239]

18. Knudsen LB, Nielsen PF, Huusfeldt PO, Johansen NL, Madsen K, Pedersen FZ, Thøgersen H, Wilken M, Agersø H. (2000) Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem, 43 (9): 1664-9. [PMID:10794683]

19. Lankat-Buttgereit B, Göke R, Fehmann HC, Richter G, Göke B. (1994) Molecular cloning of a cDNA encoding for the GLP-1 receptor expressed in rat lung. Exp Clin Endocrinol, 102 (4): 341-7. [PMID:7813606]

20. Larsen PJ, Tang-Christensen M, Jessop DS. (1997) Central administration of glucagon-like peptide-1 activates hypothalamic neuroendocrine neurons in the rat. Endocrinology, 138 (10): 4445-55. [PMID:9322962]

21. Lau J, Bloch P, Schäffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB et al.. (2015) Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem, 58 (18): 7370-80. [PMID:26308095]

22. Li B, Xi X, Roane DS, Ryan DH, Martin RJ. (2003) Distribution of glucokinase, glucose transporter GLUT2, sulfonylurea receptor-1, glucagon-like peptide-1 receptor and neuropeptide Y messenger RNAs in rat brain by quantitative real time RT-PCR. Brain Res Mol Brain Res, 113 (1-2): 139-42. [PMID:12750016]

23. MacLusky NJ, Cook S, Scrocchi L, Shin J, Kim J, Vaccarino F, Asa SL, Drucker DJ. (2000) Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling. Endocrinology, 141 (2): 752-62. [PMID:10650957]

24. Miranda LP, Winters KA, Gegg CV, Patel A, Aral J, Long J, Zhang J, Diamond S, Guido M, Stanislaus S et al.. (2008) Design and synthesis of conformationally constrained glucagon-like peptide-1 derivatives with increased plasma stability and prolonged in vivo activity. J Med Chem, 51 (9): 2758-65. [PMID:18412318]

25. Montrose-Rafizadeh C, Yang H, Rodgers BD, Beday A, Pritchette LA, Eng J. (1997) High potency antagonists of the pancreatic glucagon-like peptide-1 receptor. J Biol Chem, 272 (34): 21201-6. [PMID:9261127]

26. Nolte WM, Fortin JP, Stevens BD, Aspnes GE, Griffith DA, Hoth LR, Ruggeri RB, Mathiowetz AM, Limberakis C, Hepworth D et al.. (2014) A potentiator of orthosteric ligand activity at GLP-1R acts via covalent modification. Nat Chem Biol, 10 (8): 629-31. [PMID:24997604]

27. Nyström T, Gonon AT, Sjöholm A, Pernow J. (2005) Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism. Regul Pept, 125 (1-3): 173-7. [PMID:15582729]

28. Raufman JP, Singh L, Eng J. (1991) Exendin-3, a novel peptide from Heloderma horridum venom, interacts with vasoactive intestinal peptide receptors and a newly described receptor on dispersed acini from guinea pig pancreas. Description of exendin-3(9-39) amide, a specific exendin receptor antagonist. J Biol Chem, 266 (5): 2897-902. [PMID:1704369]

29. Runge S, Thøgersen H, Madsen K, Lau J, Rudolph R. (2008) Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain. J Biol Chem, 283 (17): 11340-7. [PMID:18287102]

30. Sebokova E, Christ AD, Wang H, Sewing S, Dong JZ, Taylor J, Cawthorne MA, Culler MD. (2010) Taspoglutide, an analog of human glucagon-like Peptide-1 with enhanced stability and in vivo potency. Endocrinology, 151 (6): 2474-82. [PMID:20382695]

31. Shughrue PJ, Lane MV, Merchenthaler I. (1996) Glucagon-like peptide-1 receptor (GLP1-R) mRNA in the rat hypothalamus. Endocrinology, 137 (11): 5159-62. [PMID:8895391]

32. Skoglund G, Hussain MA, Holz GG. (2000) Glucagon-like peptide 1 stimulates insulin gene promoter activity by protein kinase A-independent activation of the rat insulin I gene cAMP response element. Diabetes, 49: 1156-1164. [PMID:10909973]

33. Song G, Yang D, Wang Y, de Graaf C, Zhou Q, Jiang S, Liu K, Cai X, Dai A, Lin G et al.. (2017) Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators. Nature, 546 (7657): 312-315. [PMID:28514449]

34. Stoffel M, Espinosa 3rd R, Le Beau MM, Bell GI. (1993) Human glucagon-like peptide-1 receptor gene. Localization to chromosome band 6p21 by fluorescence in situ hybridization and linkage of a highly polymorphic simple tandem repeat DNA polymorphism to other markers on chromosome 6. Diabetes, 42 (8): 1215-8. [PMID:8392011]

35. Thorens B. (1992) Expression cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc Natl Acad Sci USA, 89 (18): 8641-5. [PMID:1326760]

36. Tibaduiza EC, Chen C, Beinborn M. (2001) A small molecule ligand of the glucagon-like peptide 1 receptor targets its amino-terminal hormone binding domain. J Biol Chem, 276 (41): 37787-93. [PMID:11498540]

37. Tseng CC, Zhang XY, Wolfe MM. (1999) Effect of GIP and GLP-1 antagonists on insulin release in the rat. Am J Physiol, 276 (6): E1049-54. [PMID:10362617]

38. Uttenthal LO, Blázquez E. (1990) Characterization of high-affinity receptors for truncated glucagon-like peptide-1 in rat gastric glands. FEBS Lett, 262 (1): 139-41. [PMID:2156728]

39. Véniant MM, Lu SC, Atangan L, Komorowski R, Stanislaus S, Cheng Y, Wu B, Falsey JR, Hager T, Thomas VA et al.. (2024) A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat Metab, 6 (2): 290-303. [PMID:38316982]

40. Wei Y, Mojsov S. (1995) Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett, 358 (3): 219-24. [PMID:7843404]

41. Werner U, Haschke G, Herling AW, Kramer W. (2010) Pharmacological profile of lixisenatide: A new GLP-1 receptor agonist for the treatment of type 2 diabetes. Regul Pept, 164 (2-3): 58-64. [PMID:20570597]

42. Wheeler MB, Lu M, Dillon JS, Leng XH, Chen C, Boyd 3rd AE. (1993) Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C. Endocrinology, 133 (1): 57-62. [PMID:8391428]

43. Willard FS, Wainscott DB, Showalter AD, Stutsman C, Ma W, Cardona GR, Zink RW, Corkins CM, Chen Q, Yumibe N et al.. (2021) Discovery of an Orally Efficacious Positive Allosteric Modulator of the Glucagon-like Peptide-1 Receptor. J Med Chem, 64 (6): 3439-3448. [PMID:33721487]

44. Zimmermann T, Thomas L, Baader-Pagler T, Haebel P, Simon E, Reindl W, Bajrami B, Rist W, Uphues I, Drucker DJ et al.. (2022) BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Mol Metab, 66: 101633. [PMID:36356832]

Contributors

Show »

How to cite this page