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GLP-2 receptor

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Target id: 250

Nomenclature: GLP-2 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 7 553 17p13.1 GLP2R glucagon like peptide 2 receptor 10
Mouse 7 512 11 B3 Glp2r glucagon-like peptide 2 receptor
Rat 7 550 10q24 Glp2r glucagon-like peptide 2 receptor 10
Previous and Unofficial Names Click here for help
GLP-2R
Database Links Click here for help
Specialist databases
GPCRdb glp2r_human (Hs), glp2r_mouse (Mm), glp2r_rat (Rn)
Other databases
Alphafold O95838 (Hs), Q5IXF8 (Mm), Q9Z0W0 (Rn)
CATH/Gene3D 4.10.1240.10
ChEMBL Target CHEMBL5844 (Hs), CHEMBL3822349 (Rn)
DrugBank Target O95838 (Hs)
Ensembl Gene ENSG00000065325 (Hs), ENSMUSG00000049928 (Mm), ENSRNOG00000003683 (Rn)
Entrez Gene 9340 (Hs), 93896 (Mm), 60432 (Rn)
Human Protein Atlas ENSG00000065325 (Hs)
KEGG Gene hsa:9340 (Hs), mmu:93896 (Mm), rno:60432 (Rn)
OMIM 603659 (Hs)
Pharos O95838 (Hs)
RefSeq Nucleotide NM_004246 (Hs), NM_175681 (Mm), NM_021848 (Rn)
RefSeq Protein NP_004237 (Hs), NP_783612 (Mm), NP_068620 (Rn)
UniProtKB O95838 (Hs), Q5IXF8 (Mm), Q9Z0W0 (Rn)
Wikipedia GLP2R (Hs)
Natural/Endogenous Ligands Click here for help
glucagon-like peptide 2 {Sp: Human}
glucagon-like peptide 2-(3-33) {Sp: Human}
glucagon-like peptide 2 {Sp: Mouse}
glucagon-like peptide 2-(3-33) {Sp: Mouse}
glucagon-like peptide 2-(2-33) {Sp: Rat}
glucagon-like peptide 2 {Sp: Rat}
glucagon-like peptide 2-(3-33) {Sp: Rat}

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand
Sp.
Action
Value
Parameter
Reference
glucagon-like peptide 2 {Sp: Rat} Peptide Ligand is endogenous in the given species Rn Full agonist 10.2 pKi 10
⤷ pKi 10.2 [10]
GLP-2-(1-29) (rat) Peptide Rn Partial agonist 9.5 pKi 10
⤷ pKi 9.5 [10]
[Tyr34]GLP-2 (human) Peptide Rn Full agonist 9.2 pKi 10
⤷ pKi 9.2 [10]
glucagon-like peptide 2 {Sp: Human} Peptide Rn Full agonist 8.8 pKi 10
⤷ pKi 8.8 [10]
glucagon-like peptide 2-(3-33) {Sp: Rat} Peptide Ligand is endogenous in the given species Rn Partial agonist 6.6 pKi 10
⤷ pKi 6.6 [10]
glucagon-like peptide 2-(2-33) {Sp: Rat} Peptide Ligand is endogenous in the given species Rn Partial agonist 6.1 pKi 10
⤷ pKi 6.1 [10]
GLP-2 analogue 10 Peptide Immunopharmacology Ligand Hs Agonist 10.6 pEC50 16
⤷ pEC50 10.6 (EC50 2.8x10-11 M) [16]
Description: Determined in a reporter assay using HEK293 cells stably overexpressing a cAMP response element (CRE) driven luciferase reporter and human GLP-2R.
apraglutide Peptide Hs Agonist 10.5 pEC50 7,11
⤷ pEC50 10.5 (EC50 3x10-11 M) [7,11]
glucagon-like peptide 2 {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 8.5 pIC50 12
⤷ pIC50 8.5 [12]
glucagon-like peptide 2-(3-33) {Sp: Human} Peptide Ligand is endogenous in the given species Hs Partial agonist 7.4 pIC50 12
⤷ pIC50 7.4 [12]
teduglutide Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist - - 9
⤷ [9]
View species-specific agonist tables
Agonist Comments
Glepaglutide, elsiglutide, and FE 203799 [15] are three additional DPP4-resistant GLP-2 analogues that are in clinical development:
Glepaglutide (ZP1848)- completed Phase 2 for short bowel syndrome and Phase 1 for Crohn's disease.
Elsiglutide (ZP1846)- completed Phase 2 proof-of-concept study as a preventative agent to combat chemotherapy-induced diarrhea.
Phase 1/2 FE 203799 trials for short bowel syndrome and non-Hodgkin's lymphoma (to help manage GI mucositis in patients receiving myeloablative chemotherapy) are planned but are not yet recruiting subjects (April 2018).
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
References: 
Tissue Distribution Click here for help
Isolated rat small intestine mucosal cells.
Species:  Rat
Technique:  RT-PCR.
References:  14
Highest levels found in the jejunum.
Also found in duodenum, ileum, colon and stomach.
Undetectable in the brain, heart, kidney, liver, lung, muscle and spleen.
Species:  Rat
Technique:  RNase protection assay.
References:  10
Fetal, neonatal, weaned and adult stomach.
Small and large intestines.
Jejunum, ileum and colon (higher in fetal tissues than adult).
Species:  Rat
Technique:  RT-PCR.
References:  8
Expression Datasets Click here for help

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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]

Created with Highcharts 10.3.3Log average relative​abundanceChart context menuLog average relative transcript abundance for Glp2r in mouse tissuesOlfactory epitheliumBrainstemCerebellumCerebral cortexHippocampusHypothalamusOlfactory bulbPituitary glandStriatumRetinaWhole eyeAdrenal glandIsletThyroid/ParathyroidAortaVena cavaHeart atriumHeart ventricleLungTracheaBrown adiposeKidneyLiverSkeletal muscleWhite adiposeAdipocyteTongueEsophagusGall bladderLarge intestinePancreasSmall intestineStomachUrinary bladderSpleenThymusBone marrowOvaryTestesUterusSkin01234Highcharts.com
Functional Assays Click here for help
Measurement of cAMP levels in isolated rat small intestinal mucosal cells expressing GLP-2 receptors.
Species:  Rat
Tissue:  Small intestinal mucosal cells.
Response measured:  Stimulation of cAMP production.
References:  14
Measurement of cAMP levels in COS cells transfected with the GLP-2 receptor.
Species:  Human
Tissue:  COS cells.
Response measured:  Increase in cAMP production.
References:  10
Measurement of cAMP levels in the stable GLP-2 receptor episomal expression line, rG2R.
Species:  Rat
Tissue:  rG2R episomal cell line.
Response measured:  Stimulation of cAMP production.
References:  10
Measurement of the activity of a cAMP-dependent reporter gene, CRE-β-galactosidase, in BHK cells endogenously expressing the GLP-2 receptor.
Species:  Rat
Tissue:  BHK fibroblast cells.
Response measured:  Increased activity of the reporter gene.
References:  17
Measurement of AP-1 luciferase reporter gene activity in BHK fibroblast cells endogenously expressing the GLP-2 receptor.
Species:  Rat
Tissue:  BHK fibroblast cells.
Response measured:  Induction of AP-1 luciferase activity.
References:  17
Physiological Functions Click here for help
The GLP-2 receptor-mediated small bowel growth results in an increase in nutrient digestion and absorption.
Species:  Mouse
Tissue:  In vivo.
References:  2
Promotes growth of the small intestine.
Species:  Mouse
Tissue:  Small intestine.
References:  5,13
Small bowel crypt cell proliferation.
Species:  Mouse
Tissue:  Small intestine.
References:  6
h[Gly2]GLP-2-treated mice show increased epithelial repair and reduced cell death in the crypt compartment.
Species:  Mouse
Tissue:  Small intestine.
References:  1
GLP-2 receptor activation maintains small bowel mucosal epithelium in perenteral nutrition fed rats.
Species:  Rat
Tissue:  Small intestine.
References:  3
Upregulation of small bowel hexose transport.
Species:  Rat
Tissue:  Jejunum.
References:  4
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele
Composition & genetic background
Accession
Phenotype Id
Phenotype
Reference
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0000490 abnormal crypts of Lieberkuhn morphology PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0000490 abnormal crypts of Lieberkuhn morphology PMID: 18829546 
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0000488 abnormal intestinal epithelium morphology PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0000488 abnormal intestinal epithelium morphology PMID: 18829546 
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0003448 altered tumor morphology PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0003448 altered tumor morphology PMID: 18829546 
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0002404 increased intestinal adenoma incidence PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0002404 increased intestinal adenoma incidence PMID: 18829546 
Apc+|ApcMin|Glp2r+|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2r+
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0008011 intestine polyps PMID: 18829546 
Apc+|ApcMin|Glp2rtm1Ddr ApcMin/Apc+,Glp2rtm1Ddr/Glp2rtm1Ddr
involves: C57BL/6J		 MGI:2136733  MGI:88039  MP:0008011 intestine polyps PMID: 18829546 

References

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1. Boushey RP, Yusta B, Drucker DJ. (1999) Glucagon-like peptide 2 decreases mortality and reduces the severity of indomethacin-induced murine enteritis. Am J Physiol, 277 (5): E937-47. [PMID:10567023]

2. Brubaker PL, Izzo A, Hill M, Drucker DJ. (1997) Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. Am J Physiol, 272 (6 Pt 1): E1050-8. [PMID:9227451]

3. Chance WT, Foley-Nelson T, Thomas I, Balasubramaniam A. (1997) Prevention of parenteral nutrition-induced gut hypoplasia by coinfusion of glucagon-like peptide-2. Am J Physiol, 273 (2 Pt 1): G559-63. [PMID:9277438]

4. Cheeseman CI, Tsang R. (1996) The effect of GIP and glucagon-like peptides on intestinal basolateral membrane hexose transport. Am J Physiol, 271 (3 Pt 1): G477-82. [PMID:8843773]

5. Drucker DJ, Brubaker PL. (1996) Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci USA, 93: 7911-7916. [PMID:8755576]

6. Drucker DJ, DeForest L, Brubaker PL. (1997) Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagon-like peptide 2. Am J Physiol, 273 (6): G1252-62. [PMID:9435550]

7. Hargrove DM, Alagarsamy S, Croston G, Laporte R, Qi S, Srinivasan K, Sueiras-Diaz J, Wiśniewski K, Hartwig J, Lu M et al.. (2020) Pharmacological Characterization of Apraglutide, a Novel Long-Acting Peptidic Glucagon-Like Peptide-2 Agonist, for the Treatment of Short Bowel Syndrome. J Pharmacol Exp Ther, 373 (2): 193-203. [PMID:32075870]

8. Lovshin J, Yusta B, Iliopoulos I, Migirdicyan A, Dableh L, Brubaker PL, Drucker DJ. (2000) Ontogeny of the glucagon-like peptide-2 receptor axis in the developing rat intestine. Endocrinology, 141 (11): 4194-201. [PMID:11089553]

9. McKeage K. (2015) Teduglutide: a guide to its use in short bowel syndrome. Clin Drug Investig, 35 (5): 335-40. [PMID:25859983]

10. Munroe DG, Gupta AK, Kooshesh F, Vyas TB, Rizkalla G, Wang H, Demchyshyn L, Yang ZJ, Kamboj RK, Chen H et al.. (1999) Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2. Proc Natl Acad Sci USA, 96 (4): 1569-73. [PMID:9990065]

11. Slim GM, Lansing M, Wizzard P, Nation PN, Wheeler SE, Brubaker PL, Jeppesen PB, Wales PW, Turner JM. (2019) Novel Long-Acting GLP-2 Analogue, FE 203799 (Apraglutide), Enhances Adaptation and Linear Intestinal Growth in a Neonatal Piglet Model of Short Bowel Syndrome with Total Resection of the Ileum. JPEN J Parenter Enteral Nutr, 43 (7): 891-898. [PMID:30614011]

12. Thulesen J, Knudsen LB, Hartmann B, Hastrup S, Kissow H, Jeppesen PB, Ørskov C, Holst JJ, Poulsen SS. (2002) The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. Regul Pept, 103 (1): 9-15. [PMID:11738243]

13. Tsai CH, Hill M, Asa SL, Brubaker PL, Drucker DJ. (1997) Intestinal growth-promoting properties of glucagon-like peptide-2 in mice. Am J Physiol, 273 (1 Pt 1): E77-84. [PMID:9252482]

14. Walsh NA, Yusta B, DaCambra MP, Anini Y, Drucker DJ, Brubaker PL. (2003) Glucagon-like peptide-2 receptor activation in the rat intestinal mucosa. Endocrinology, 144 (10): 4385-92. [PMID:12960094]

15. Wiśniewski K, Sueiras-Diaz J, Jiang G, Galyean R, Lu M, Thompson D, Wang YC, Croston G, Posch A, Hargrove DM et al.. (2016) Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance. J Med Chem, 59 (7): 3129-39. [PMID:26986178]

16. Yang PY, Zou H, Lee C, Muppidi A, Chao E, Fu Q, Luo X, Wang D, Schultz PG, Shen W. (2018) Stapled, Long-Acting Glucagon-like Peptide 2 Analog with Efficacy in Dextran Sodium Sulfate Induced Mouse Colitis Models. J Med Chem, 61 (7): 3218-3223. [PMID:29528634]

17. Yusta B, Somwar R, Wang F, Munroe D, Grinstein S, Klip A, Drucker DJ. (1999) Identification of glucagon-like peptide-2 (GLP-2)-activated signaling pathways in baby hamster kidney fibroblasts expressing the rat GLP-2 receptor. J Biol Chem, 274 (43): 30459-67. [PMID:10521425]

Contributors

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How to cite this page

Bataille D, Chan SL, Delagrange P, Drucker DJ, Göke B, Hills R, Mayo KE, Miller LJ, Salvatori R, Thorens B. Glucagon receptor family in GtoPdb v.2023.1. IUPHAR/BPS Guide to Pharmacology CITE. 2023; 2023(1). Available from: https://doi.org/10.2218/gtopdb/F29/2023.1.