Glucagon-like peptide 1 receptor

The glucagon-like peptide 1 receptor (GLP1R) is a human gene which resides on chromosome 6.cite journal | author = Thorens B | title = Expression cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 89 | issue = 18 | pages = 8641–5 | year = 1992 | month = September | pmid = 1326760 | pmc = 49976 | url = | doi = 10.1073/pnas.89.18.8641 ] cite journal | author = Dillon JS, Tanizawa Y, Wheeler MB, Leng XH, Ligon BB, Rabin DU, Yoo-Warren H, Permutt MA, Boyd AE 3rd | title = Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor | journal = Endocrinology | volume = 133 | issue = 4 | pages = 1907–10 | year = 1993 | month = October | pmid = 8404634 | url = | doi = 10.1210/en.133.4.1907 ] The protein encoded by this gene is a member of the glucagon receptor family of G protein-coupled receptors.cite journal | author = Brubaker PL, Drucker DJ | title = Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors | journal = Recept. Channels | volume = 8 | issue = 3-4 | pages = 179–88 | year = 2002 | pmid = 12529935| url = http://www.glucagon.com/pdfs/Receptors%20and%20Channels.pdf | accessdate = 2008-07-14 | doi = 10.1080/10606820213687 ]

Ligand specificity

GLP1R binds specifically the glucagon-like peptide-1 (GLP1) and has much lower affinity for related peptides such as the gastric inhibitory polypeptide and glucagon.cite journal | author = Fehmann HC, Jiang J, Schweinfurth J, Dörsch K, Wheeler MB, Boyd AE 3rd, Göke B | title = Ligand-specificity of the rat GLP-I receptor recombinantly expressed in Chinese hamster ovary (CHO-) cells | journal = Z Gastroenterol | volume = 32 | issue = 4 | pages = 203–7 | year = 1994 | month = April | pmid = 8017094 | url = | issn = ]

Function and therapeutic potential

GLP1R is known to be expressed in pancreatic beta cells. Activated GLP1R stimulates the adenylyl cyclase pathway which results in increased insulin synthesis and release of insulin.cite journal | author = Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF | title = Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 84 | issue = 10 | pages = 3434–8 | year = 1987 | month = May | pmid = 3033647 | pmc = 304885 | url = | doi = 10.1073/pnas.84.10.3434 ] Consequently GLP1R has been suggested as a potential target for the treatment of diabetes.cite journal | author = Holst JJ | title = Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors | journal = Expert Opin Emerg Drugs | volume = 9 | issue = 1 | pages = 155–66 | year = 2004 | month = May | pmid = 15155141 | doi = 10.1517/eoed.9.1.155.32952 | url = ]

GLP1R is also expressed in the brain where it is involved in the control of appetite.cite journal | author = Kinzig KP, D'Alessio DA, Seeley RJ | title = The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness | journal = J. Neurosci. | volume = 22 | issue = 23 | pages = 10470–6 | year = 2002 | month = December | pmid = 12451146 | url = http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=12451146 | issn = ] Furthermore, mice which over express GLP1R display improved memory and learning.cite journal | author = During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN | title = Glucagon-like peptide-1 receptor is involved in learning and neuroprotection | journal = Nat. Med. | volume = 9 | issue = 9 | pages = 1173–9 | year = 2003 | month = September | pmid = 12925848 | doi = 10.1038/nm919 | url = ]

ee also

* Glucagon-like peptide-1
* Dipeptidyl peptidase-4

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=van Eyll B, Lankat-Buttgereit B, Bode HP, "et al." |title=Signal transduction of the GLP-1-receptor cloned from a human insulinoma |journal=FEBS Lett. |volume=348 |issue= 1 |pages= 7–13 |year= 1994 |pmid= 7517895 |doi=
*cite journal | author=Gromada J, Rorsman P, Dissing S, Wulff BS |title=Stimulation of cloned human glucagon-like peptide 1 receptor expressed in HEK 293 cells induces cAMP-dependent activation of calcium-induced calcium release |journal=FEBS Lett. |volume=373 |issue= 2 |pages= 182–6 |year= 1995 |pmid= 7589461 |doi=
*cite journal | author=Wei Y, Mojsov S |title=Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences |journal=FEBS Lett. |volume=358 |issue= 3 |pages= 219–24 |year= 1995 |pmid= 7843404 |doi=
*cite journal | author=Lankat-Buttgereit B, Göke R, Stöckmann F, "et al." |title=Detection of the human glucagon-like peptide 1(7-36) amide receptor on insulinoma-derived cell membranes |journal=Digestion |volume=55 |issue= 1 |pages= 29–33 |year= 1994 |pmid= 8112494 |doi=
*cite journal | author=Graziano MP, Hey PJ, Borkowski D, "et al." |title=Cloning and functional expression of a human glucagon-like peptide-1 receptor |journal=Biochem. Biophys. Res. Commun. |volume=196 |issue= 1 |pages= 141–6 |year= 1993 |pmid= 8216285 |doi= 10.1006/bbrc.1993.2226
*cite journal | author=Stoffel M, Espinosa R, Le Beau MM, Bell GI |title=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 |journal=Diabetes |volume=42 |issue= 8 |pages= 1215–8 |year= 1993 |pmid= 8392011 |doi=
*cite journal | author=Dillon JS, Tanizawa Y, Wheeler MB, "et al." |title=Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor |journal=Endocrinology |volume=133 |issue= 4 |pages= 1907–10 |year= 1993 |pmid= 8404634 |doi=
*cite journal | author=Thorens B, Porret A, Bühler L, "et al." |title=Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor |journal=Diabetes |volume=42 |issue= 11 |pages= 1678–82 |year= 1993 |pmid= 8405712 |doi=
*cite journal | author=Lankat-Buttgereit B, Göke B |title=Cloning and characterization of the 5' flanking sequences (promoter region) of the human GLP-1 receptor gene |journal=Peptides |volume=18 |issue= 5 |pages= 617–24 |year= 1997 |pmid= 9213353 |doi=
*cite journal | author=Frimurer TM, Bywater RP |title=Structure of the integral membrane domain of the GLP1 receptor |journal=Proteins |volume=35 |issue= 4 |pages= 375–86 |year= 1999 |pmid= 10382665 |doi=
*cite journal | author=Huypens P, Ling Z, Pipeleers D, Schuit F |title=Glucagon receptors on human islet cells contribute to glucose competence of insulin release |journal=Diabetologia |volume=43 |issue= 8 |pages= 1012–9 |year= 2001 |pmid= 10990079 |doi=
*cite journal | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi=
*cite journal | author=Xiao Q, Jeng W, Wheeler MB |title=Characterization of glucagon-like peptide-1 receptor-binding determinants |journal=J. Mol. Endocrinol. |volume=25 |issue= 3 |pages= 321–35 |year= 2001 |pmid= 11116211 |doi=
*cite journal | author=Bazarsuren A, Grauschopf U, Wozny M, "et al." |title=In vitro folding, functional characterization, and disulfide pattern of the extracellular domain of human GLP-1 receptor |journal=Biophys. Chem. |volume=96 |issue= 2-3 |pages= 305–18 |year= 2003 |pmid= 12034449 |doi=
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Mungall AJ, Palmer SA, Sims SK, "et al." |title=The DNA sequence and analysis of human chromosome 6 |journal=Nature |volume=425 |issue= 6960 |pages= 805–11 |year= 2003 |pmid= 14574404 |doi= 10.1038/nature02055
*cite journal | author=Tokuyama Y, Matsui K, Egashira T, "et al." |title=Five missense mutations in glucagon-like peptide 1 receptor gene in Japanese population |journal=Diabetes Res. Clin. Pract. |volume=66 |issue= 1 |pages= 63–9 |year= 2005 |pmid= 15364163 |doi= 10.1016/j.diabres.2004.02.004
*cite journal | author=Gerhard DS, Wagner L, Feingold EA, "et al." |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504
*cite journal | author=Jorgensen R, Martini L, Schwartz TW, Elling CE |title=Characterization of glucagon-like peptide-1 receptor beta-arrestin 2 interaction: a high-affinity receptor phenotype |journal=Mol. Endocrinol. |volume=19 |issue= 3 |pages= 812–23 |year= 2005 |pmid= 15528268 |doi= 10.1210/me.2004-0312
*cite journal | author=Mahon MJ, Shimada M |title=Calmodulin interacts with the cytoplasmic tails of the parathyroid hormone 1 receptor and a sub-set of class b G-protein coupled receptors |journal=FEBS Lett. |volume=579 |issue= 3 |pages= 803–7 |year= 2005 |pmid= 15670850 |doi= 10.1016/j.febslet.2004.12.056

External links

* [http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2288 IUPHAR GPCR Database - GLP-1 receptor]
*

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