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Gene Review

Glp1r  -  glucagon-like peptide 1 receptor

Mus musculus

Synonyms: GLP-1 receptor, GLP-1-R, GLP-1R, GLP1Rc, Glucagon-like peptide 1 receptor
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Disease relevance of Glp1r


Psychiatry related information on Glp1r

  • To determine the physiological importance of GLP-1 receptor (GLP-1R)-leptin interactions, we studied islet function and feeding behavior in ob/ob:GLP-1R(-/-) mice [4].
  • As glucagon-like peptide-1 receptor agonism has been found to elicit behaviors associated with visceral illness in rodents, we also examined the effect of peripheral exenatide on kaolin consumption and locomotor activity [5].

High impact information on Glp1r

  • These GLP1R-/- mice are viable, develop normally but exhibit increased levels of blood glucose following oral glucose challenge in association with diminished levels of circulating insulin [1].
  • Two substituted cyclobutanes (S4P and Boc5) were developed after screening a compound library against a cell line stably cotransfected with GLP-1R and a cAMP-responsive reporter [6].
  • Despite full recovery of beta-cell mass after 50% partial pancreatectomy (Ppx) in BALB/c mice, no pancreatic Ngn3 immunoreactivity was detected, even when the beta-cell trophic glucagon-like peptide-1 receptor agonist exendin-4 was administered after the procedure [7].
  • We determined the role of the islet beta-cell and the pancreatic duodenal homeobox-1 (Pdx1) transcription factor for GLP-1 receptor (GLP-1R)-dependent actions through analysis of mice with beta-cell-specific inactivation of the Pdx1 gene (beta-cell(Pdx1-/-) mice) [8].
  • These findings demonstrate that Pdx1 expression is essential for integrating GLP-1R-dependent signals regulating alpha-cell glucagon secretion and for the growth, differentiated function, and survival of islet beta-cells [8].

Chemical compound and disease context of Glp1r


Biological context of Glp1r


Anatomical context of Glp1r


Associations of Glp1r with chemical compounds


Other interactions of Glp1r

  • In contrast, no significant perturbation in the insulin response to perfused glucagon was detected under conditions of low (4.4 mmol/l) or high (16.6 mmol/l) glucose in GLP-1R -/- mice [20].
  • Serum GIP levels in GLP-1R -/- mice were significantly elevated versus those in +/+ control mice after an oral glucose tolerance test (369 +/- 40 vs. 236 +/- 28 pmol/l; P < or = 0.02) [20].
  • Despite the demonstration that GLP-1 stimulates proinsulin gene transcription, pancreatic insulin mRNA transcripts were similar in wild-type and GLP-1R -/- mice [21].
  • In contrast, GIPR Ab had no effect on glucose excursion or insulin secretion, after ip glucose challenge, in +/+ or GLP-1R-/- mice [22].
  • These data suggest multiple modes of action of OXM: 1) it directly elevates murine intrinsic HR through a GLP-1R-independent mechanism, perhaps via the glucagon receptor or an unidentified OXM receptor, and 2) it lowers food intake, activity, and T(b) in a GLP-1R-dependent fashion [23].

Analytical, diagnostic and therapeutic context of Glp1r


  1. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Scrocchi, L.A., Brown, T.J., MaClusky, N., Brubaker, P.L., Auerbach, A.B., Joyner, A.L., Drucker, D.J. Nat. Med. (1996) [Pubmed]
  2. Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5'-adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol 3-kinase-dependent pathway. Hui, H., Nourparvar, A., Zhao, X., Perfetti, R. Endocrinology (2003) [Pubmed]
  3. The murine glucagon-like peptide-1 receptor is essential for control of bone resorption. Yamada, C., Yamada, Y., Tsukiyama, K., Yamada, K., Udagawa, N., Takahashi, N., Tanaka, K., Drucker, D.J., Seino, Y., Inagaki, N. Endocrinology (2008) [Pubmed]
  4. Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action. Scrocchi, L.A., Hill, M.E., Saleh, J., Perkins, B., Drucker, D.J. Diabetes (2000) [Pubmed]
  5. Antiobesity action of peripheral exenatide (exendin-4) in rodents: effects on food intake, body weight, metabolic status and side-effect measures. Mack, C.M., Moore, C.X., Jodka, C.M., Bhavsar, S., Wilson, J.K., Hoyt, J.A., Roan, J.L., Vu, C., Laugero, K.D., Parkes, D.G., Young, A.A. International journal of obesity (2005) (2006) [Pubmed]
  6. A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db/db mice. Chen, D., Liao, J., Li, N., Zhou, C., Liu, Q., Wang, G., Zhang, R., Zhang, S., Lin, L., Chen, K., Xie, X., Nan, F., Young, A.A., Wang, M.W. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  7. Regeneration of pancreatic islets after partial pancreatectomy in mice does not involve the reactivation of neurogenin-3. Lee, C.S., De León, D.D., Kaestner, K.H., Stoffers, D.A. Diabetes (2006) [Pubmed]
  8. beta-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. Li, Y., Cao, X., Li, L.X., Brubaker, P.L., Edlund, H., Drucker, D.J. Diabetes (2005) [Pubmed]
  9. Effects of aging and a high fat diet on body weight and glucose tolerance in glucagon-like peptide-1 receptor -/- mice. Scrocchi, L.A., Drucker, D.J. Endocrinology (1998) [Pubmed]
  10. Chronic exposure to GLP-1R agonists promotes homologous GLP-1 receptor desensitization in vitro but does not attenuate GLP-1R-dependent glucose homeostasis in vivo. Baggio, L.L., Kim, J.G., Drucker, D.J. Diabetes (2004) [Pubmed]
  11. New developments in the biology of the glucagon-like peptides GLP-1 and GLP-2. Drucker, D.J., Lovshin, J., Baggio, L., Nian, M., Adatia, F., Boushey, R.P., Liu, Y., Saleh, J., Yusta, B., Scrocchi, L. Ann. N. Y. Acad. Sci. (2000) [Pubmed]
  12. Quantitative trait loci for carbohydrate and total energy intake on mouse chromosome 17: congenic strain confirmation and candidate gene analyses (Glo1, Glp1r). Kumar, K.G., Poole, A.C., York, B., Volaufova, J., Zuberi, A., Richards, B.K. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2007) [Pubmed]
  13. Mouse pancreatic beta-cells exhibit preserved glucose competence after disruption of the glucagon-like peptide-1 receptor gene. Flamez, D., Van Breusegem, A., Scrocchi, L.A., Quartier, E., Pipeleers, D., Drucker, D.J., Schuit, F. Diabetes (1998) [Pubmed]
  14. Novel signal transduction and peptide specificity of glucagon-like peptide receptor in 3T3-L1 adipocytes. Montrose-Rafizadeh, C., Yang, H., Wang, Y., Roth, J., Montrose, M.H., Adams, L.G. J. Cell. Physiol. (1997) [Pubmed]
  15. Glucagon-like peptide-1(7-36) amide (GLP-1) enhances insulin-stimulated glucose metabolism in 3T3-L1 adipocytes: one of several potential extrapancreatic sites of GLP-1 action. Egan, J.M., Montrose-Rafizadeh, C., Wang, Y., Bernier, M., Roth, J. Endocrinology (1994) [Pubmed]
  16. Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Gros, R., You, X., Baggio, L.L., Kabir, M.G., Sadi, A.M., Mungrue, I.N., Parker, T.G., Huang, Q., Drucker, D.J., Husain, M. Endocrinology (2003) [Pubmed]
  17. Glucagon Receptor Knockout Mice Display Increased Insulin Sensitivity and Impaired {beta}-Cell Function. S??rensen, H., Winzell, M.S., Brand, C.L., Fosgerau, K., Gelling, R.W., Nishimura, E., Ahren, B. Diabetes (2006) [Pubmed]
  18. Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling. MacLusky, N.J., Cook, S., Scrocchi, L., Shin, J., Kim, J., Vaccarino, F., Asa, S.L., Drucker, D.J. Endocrinology (2000) [Pubmed]
  19. A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic beta cells. Kang, G., Chepurny, O.G., Rindler, M.J., Collis, L., Chepurny, Z., Li, W.H., Harbeck, M., Roe, M.W., Holz, G.G. J. Physiol. (Lond.) (2005) [Pubmed]
  20. Enhanced glucose-dependent insulinotropic polypeptide secretion and insulinotropic action in glucagon-like peptide 1 receptor -/- mice. Pederson, R.A., Satkunarajah, M., McIntosh, C.H., Scrocchi, L.A., Flamez, D., Schuit, F., Drucker, D.J., Wheeler, M.B. Diabetes (1998) [Pubmed]
  21. Identification of glucagon-like peptide 1 (GLP-1) actions essential for glucose homeostasis in mice with disruption of GLP-1 receptor signaling. Scrocchi, L.A., Marshall, B.A., Cook, S.M., Brubaker, P.L., Drucker, D.J. Diabetes (1998) [Pubmed]
  22. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, regulates fasting glycemia and nonenteral glucose clearance in mice. Baggio, L., Kieffer, T.J., Drucker, D.J. Endocrinology (2000) [Pubmed]
  23. Oxyntomodulin increases intrinsic heart rate in mice independent of the glucagon-like peptide-1 receptor. Sowden, G.L., Drucker, D.J., Weinshenker, D., Swoap, S.J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2007) [Pubmed]
  24. Glucagon and glucagon-like peptide receptors as drug targets. Estall, J.L., Drucker, D.J. Curr. Pharm. Des. (2006) [Pubmed]
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