This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Drucker, D. J. Search for Related Content PubMed PubMed Citation Articles by Drucker, D. J.

Glucagon-Like Peptide 2¹

Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada M5G 2C4

Address correspondence and requests for reprints to: Dr. D. J. Drucker, Toronto General Hospital, 101 College Street CCRW3-845, Toronto, Ontario, Canada M5G 2C4. E-mail: d.drucker{at}utoronto.ca

Glucagon-like peptide 2 (GLP-2) is a 33 amino acid peptide-encoded carboxyterminal to the sequence of GLP-1 in the proglucagon gene. Both GLP-1 and GLP-2 are secreted from gut endocrine cells and promote nutrient absorption through distinct mechanisms of action. GLP-2 regulates gastric motility, gastric acid secretion, intestinal hexose transport, and increases the barrier function of the gut epithelium. GLP-2 significantly enhances the surface area of the mucosal epithelium via stimulation of crypt cell proliferation and inhibition of apoptosis in the enterocyte and crypt compartments. The cytoprotective and reparative effects of GLP-2 are evident in rodent models of experimental intestinal injury. GLP-2 reduces mortality and decreases mucosal injury, cytokine expression, and bacterial septicemia in the setting of small and large bowel inflammation. GLP-2 also enhances nutrient absorption and gut adaptation in rodents or humans with short bowel syndrome. The actions of GLP-2 are transduced by the GLP-2 receptor, a G protein-coupled receptor expressed in gut endocrine cells of the stomach, small bowel, and colon. Activation of GLP-2 receptor signaling in heterologous cells promotes resistance to apoptotic injury in vitro. The cytoprotective, reparative, and energy-retentive properties of GLP-2 suggests that GLP-2 may potentially be useful for the treatment of human disorders characterized by injury and/or dysfunction of the intestinal mucosal epithelium.

This article has been cited by other articles:

				E. A. Ozer, J. J. Holst, N. Duman, A. Kumral, and H. Ozkan The Relationship between Glucagon-Like Peptide 2 and Feeding Intolerance in Preterm Infants J Trop Pediatr, August 1, 2009; 55(4): 276 - 277. [Abstract] [Full Text] [PDF]

				M. Metwally, S. Amer, T.C. Li, and W.L. Ledger An RCT of metformin versus orlistat for the management of obese anovulatory women Hum. Reprod., April 1, 2009; 24(4): 966 - 975. [Abstract] [Full Text] [PDF]

				D. B. Henriksen The Gut Feeling of Bone Remodeling IBMS BoneKEy, November 1, 2005; 2(11): 16 - 23. [Full Text] [PDF]

				A. Dey, G. M. Lipkind, Y. Rouille, C. Norrbom, J. Stein, C. Zhang, R. Carroll, and D. F. Steiner Significance of Prohormone Convertase 2, PC2, Mediated Initial Cleavage at the Proglucagon Interdomain Site, Lys70-Arg71, to Generate Glucagon Endocrinology, February 1, 2005; 146(2): 713 - 727. [Abstract] [Full Text] [PDF]

				J. A. Lovshin, Q. Huang, R. Seaberg, P. L. Brubaker, and D. J. Drucker Extrahypothalamic Expression of the Glucagon-Like Peptide-2 Receptor Is Coupled to Reduction of Glutamate-Induced Cell Death in Cultured Hippocampal Cells Endocrinology, July 1, 2004; 145(7): 3495 - 3506. [Abstract] [Full Text] [PDF]

				A. Ramsanahie, M. S. Duxbury, T. C. Grikscheit, A. Perez, D. B. Rhoads, J. Gardner-Thorpe, J. Ogilvie, S. W. Ashley, J. P. Vacanti, and E. E. Whang Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine Am J Physiol Gastrointest Liver Physiol, December 1, 2003; 285(6): G1345 - G1352. [Abstract] [Full Text] [PDF]

				R. Gros, X. You, L. L. Baggio, M. G. Kabir, A. M. Sadi, I. N. Mungrue, T. G. Parker, Q. Huang, D. J. Drucker, and M. Husain Cardiac Function in Mice Lacking the Glucagon-Like Peptide-1 Receptor Endocrinology, June 1, 2003; 144(6): 2242 - 2252. [Abstract] [Full Text] [PDF]

				Y. M. Petersen, B. Hartmann, J. J. Holst, I. Le Huerou-Luron, C. R. Bjornvad, and P. T. Sangild Introduction of Enteral Food Increases Plasma GLP-2 and Decreases GLP-2 Receptor mRNA Abundance during Pig Development J. Nutr., June 1, 2003; 133(6): 1781 - 1786. [Abstract] [Full Text] [PDF]

				X. Cao, G. Flock, C. Choi, D. M. Irwin, and D. J. Drucker Aberrant Regulation of Human Intestinal Proglucagon Gene Expression in the NCI-H716 Cell Line Endocrinology, May 1, 2003; 144(5): 2025 - 2033. [Abstract] [Full Text] [PDF]

				K. E. Mayo, L. J. Miller, D. Bataille, S. Dalle, B. Goke, B. Thorens, and D. J. Drucker International Union of Pharmacology. XXXV. The Glucagon Receptor Family Pharmacol. Rev., March 1, 2003; 55(1): 167 - 194. [Abstract] [Full Text] [PDF]

				D. J. Drucker Glucagon-Like Peptides: Regulators of Cell Proliferation, Differentiation, and Apoptosis Mol. Endocrinol., February 1, 2003; 17(2): 161 - 171. [Abstract] [Full Text] [PDF]

				D. K.Y. Trinh, K. Zhang, M. Hossain, P. L. Brubaker, and D. J. Drucker Pax-6 Activates Endogenous Proglucagon Gene Expression in the Rodent Gastrointestinal Epithelium Diabetes, February 1, 2003; 52(2): 425 - 433. [Abstract] [Full Text] [PDF]

				Y. Li, T. Hansotia, B. Yusta, F. Ris, P. A. Halban, and D. J. Drucker Glucagon-like Peptide-1 Receptor Signaling Modulates beta Cell Apoptosis J. Biol. Chem., January 3, 2003; 278(1): 471 - 478. [Abstract] [Full Text] [PDF]

				X. Zhu, A. Zhou, A. Dey, C. Norrbom, R. Carroll, C. Zhang, V. Laurent, I. Lindberg, R. Ugleholdt, J. J. Holst, et al. Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects PNAS, August 6, 2002; 99(16): 10293 - 10298. [Abstract] [Full Text] [PDF]

				B. Yusta, J. Estall, and D. J. Drucker Glucagon-like Peptide-2 Receptor Activation Engages Bad and Glycogen Synthase Kinase-3 in a Protein Kinase A-dependent Manner and Prevents Apoptosis following Inhibition of Phosphatidylinositol 3-Kinase J. Biol. Chem., July 5, 2002; 277(28): 24896 - 24906. [Abstract] [Full Text] [PDF]