The "cryptic" mechanism of action of glucagon-like peptide-2

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 301, Issue 1, 2011, Pages

  Rowland, Katherine J ^a   Brubaker, Patricia L ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Colon cancer; Growth factors; Intestine; Proliferation; Stem cells

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; GLUCAGON LIKE PEPTIDE 2; KERATINOCYTE GROWTH FACTOR; NITRIC OXIDE; PREBIOTIC AGENT; SOMATOMEDIN B; SOMATOMEDIN C; SOMATOMEDIN C RECEPTOR; TEDUGLUTIDE; VASOACTIVE INTESTINAL POLYPEPTIDE;

ABSORPTION; ANTIINFLAMMATORY ACTIVITY; BLOOD FLOW; CELL PROLIFERATION; COLON; COLON CANCER; CROHN DISEASE; CRYPT CELL; DIGESTION; DRUG MECHANISM; GASTROINTESTINAL TRACT; HUMAN; INTESTINE; INTESTINE CELL; MYOFIBROBLAST; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; REVIEW; SHORT BOWEL SYNDROME; SMALL INTESTINE;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; COLONIC NEOPLASMS; FIBROBLAST GROWTH FACTOR 7; GLUCAGON-LIKE PEPTIDE 2; HUMANS; INTESTINES; MICE; NITRIC OXIDE; RATS; RECEPTORS, GLUCAGON; SIGNAL TRANSDUCTION; SOMATOMEDINS; STEM CELLS; VASOACTIVE INTESTINAL PEPTIDE;

EID: 79959845565     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00039.2011     Document Type: Review

References (79)

1. Ahmad T, Farnie G, Bundred NJ, Anderson NG. The mitogenic action of insulin-like growth factor I in normal human mammary epithelial cells requires the epidermal growth factor receptor tyrosine kinase. J Biol Chem 279: 1713-1719, 2004.
2. Anini Y, Izzo A, Oudit GY, Backx PH, Brubaker PL. Role of phosphatidylinositol- 3 kinase-γ in the actions of glucagon-like peptide-2 on the murine small intestine. Am J Physiol Endocrinol Metab 292: E1599- E1606, 2007.
3. Bahrami J, Longuet C, Baggio LL, Li K, Drucker DJ. Glucagon-like peptide-2 receptor modulates islet adaptation to metabolic stress in the ob/ob mouse. Gastroenterology 139: 857-868, 2010.
4. Bahrami J, Yusta B, Drucker DJ. ErbB activity links the glucagon-like peptide-2 receptor to refeeding-induced adaptation in the murine small bowel. Gastroenterology 138: 2447-2456, 2010.
5. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449: 1003-1007, 2007.
6. Bjerknes M, Cheng H. Modulation of specific intestinal epithelial progenitors by enteric neurons. Proc Natl Acad Sci USA 98: 12497-12502, 2001.
7. Booth C, Booth D, Williamson S, Demchyshyn LL, Potten CS. Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage. Cell Prolif 37: 385-400, 2004
8. Bremholm L, Hornum M, Henriksen BM, Larsen S, Holst JJ. Glucagon- like peptide-2 increases mesenteric blood flow in humans. Scand J Gastroenterol 44: 314-319, 2009.
9. Brubaker PL, Izzo A, Hill M, Drucker DJ. Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. Am J Physiol Endocrinol Metab 272: E1050-E1058, 1997.
10. Buchman AL, Katz S, Fang JC, Bernstein CN, Abou-Assi SG. Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2) for the treatment of moderate to severe Crohn's disease. Inflamm Bowel Dis 16: 962-973, 2010.
11. Burrin DG, Stoll B, Guan X, Cui L, Chang X, Hadsell D. GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets. Am J Physiol Endocrinol Metab 292: E281-E291, 2007.
12. Cameron HL, Perdue MH. Stress impairs murine intestinal barrier function: improvement by glucagon-like peptide-2. J Pharmacol Exp Ther 314: 214-220, 2005.
13. Cameron HL, Yang PC, Perdue MH. Glucagon-like peptide-2-enhanced barrier function reduces pathophysiology in a model of food allergy. Am J Physiol Gastrointest Liver Physiol 284: G905-G912, 2003.
14. Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58: 1091-1103, 2009.
15. Cheeseman CI. Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo. Am J Physiol Regul Integr Comp Physiol 273: R1965-R1971, 1997.
16. Coppola D, Ferber A, Miura M, Sell C, D'Ambrosio C, Rubin R, Baserga R. A functional insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the epidermal growth factor receptor. Mol Cell Biol 14: 4588-4595, 1994.
17. Dhanvantari S, Seidah NG, Brubaker PL. Role of prohormone convertases in the tissue-specific processing of proglucagon. Mol Endocrinol 10: 342-355, 1996.
18. Drucker DJ, DeForest L, Brubaker PL. Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagonlike peptide 2. Am J Physiol Gastrointest Liver Physiol 273: G1252-G1262, 1997.
19. Drucker DJ, Erlich P, Asa SL, Brubaker PL. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci USA 93: 7911-7916, 1996.
20. Dube PE, Brubaker PL. Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators. Am J Physiol Endocrinol Metab 293: E460-E465, 2007.
21. Dube PE, Forse CL, Bahrami J, Brubaker PL. The essential role of insulin-like growth factor-1 in the intestinal tropic effects of glucagon-like peptide-2 in mice. Gastroenterology 131: 589-605, 2006.
22. Dube PE, Rowland KJ, Brubaker PL. Glucagon-like peptide-2 activates beta-catenin signaling in the mouse intestinal crypt: role of insulin-like growth factor-I. Endocrinology 149: 291-301, 2008.
23. Estall JL, Drucker DJ. Glucagon-like peptide-2. Annu Rev Nutr 26: 391-411, 2006.
24. Garrison AP, Dekaney CM, von Allmen DC, Lund PK, Henning SJ, Helmrath MA. Early but not late administration of glucagon-like peptide- 2 following ileo-cecal resection augments putative intestinal stem cell expansion. Am J Physiol Gastrointest Liver Physiol 296: G643-G650, 2009.
25. Gayer CP, Chaturvedi LS, Wang S, Craig DH, Flanigan T, Basson MD. Strain-induced proliferation requires the phosphatidylinositol 3-kinase/ AKT/glycogen synthase kinase pathway. J Biol Chem 284: 2001-2011, 2009.
26. Gleeson MH, Bloom SR, Polak JM, Henry K, Dowling RH. Endocrine tumour in kidney affecting small bowel structure, motility, and absorptive function. Gut 12: 773-782, 1971.
27. Gschwind A, Zwick E, Prenzel N, Leserer M, Ullrich A. Cell communication networks: epidermal growth factor receptor transactivation as the paradigm for interreceptor signal transmission. Oncogene 20: 1594-1600, 2001.
28. Guan X, Karpen HE, Stephens J, Bukowski JT, Niu S, Zhang G, Stoll B, Finegold MJ, Holst JJ, Hadsell D, Nichols BL, Burrin DG. GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow. Gastroenterology 130: 150-164, 2006.
29. Guan X, Stoll B, Lu X, Tappenden KA, Holst JJ, Hartmann B, Burrin DG. GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1. Gastroenterology 125: 136-147, 2003.
30. Hadjiyanni I, Li KK, Drucker DJ. Glucagon-like peptide-2 reduces intestinal permeability but does not modify the onset of type 1 diabetes in the nonobese diabetic mouse. Endocrinology 150: 592-599, 2009.
31. Hare KJ, Hartmann B, Kissow H, Holst JJ, Poulsen SS. The intestinotrophic peptide, glp-2, counteracts intestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, gefitinib. Clin Cancer Res 13: 5170-5175, 2007.
32. Hartmann B, Thulesen J, Hare KJ, Kissow H, Orskov C, Poulsen SS, Holst JJ. Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive intestinal growth in diabetic rats. Regul Pept 105: 173-179, 2002.
33. He XC, Yin T, Grindley JC, Tian Q, Sato T, Tao WA, Dirisina R, Porter-Westpfahl KS, Hembree M, Johnson T, Wiedemann LM, Barrett TA, Hood L, Wu H, Li L. PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat Genet 39: 189-198, 2007.
34. Helmrath MA, Erwin CR, Warner BW. A defective EGF-receptor in waved-2 mice attenuates intestinal adaptation. J Surg Res 69: 76-80, 1997.
35. Hsieh J, Longuet C, Maida A, Bahrami J, Xu E, Baker CL, Brubaker PL, Drucker DJ, Adeli K. Glucagon-like peptide-2 increases intestinal lipid absorption and chylomicron production via CD36. Gastroenterology 137: 997-1005, 1005.e1-4, 2009.
36. Iakoubov R, Lauffer LM, Trivedi S, Kim YI, Brubaker PL. Carcinogenic effects of exogenous and endogenous glucagon-like peptide-2 in azoxymethane-treated mice. Endocrinology 150: 4033-4043, 2009.
37. Ivory CP, Wallace LE, McCafferty DM, Sigalet DL. Interleukin-10- independent anti-inflammatory actions of glucagon-like peptide 2. Am J Physiol Gastrointest Liver Physiol 295: G1202-G1210, 2008.
38. Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O'Keefe SJ. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut 2011 Feb 11. [Epub ahead of print] doi: 10.11.1136/gut.2010.218271.
39. Jeppesen PB, Lund P, Gottschalck IB, Nielsen HB, Holst JJ, Mortensen J, Poulsen SS, Quistorff B, Mortensen PB. Short bowel patients treated for two years with glucagon-like peptide 2: effects on intestinal morphology and absorption, renal function, bone and body composition, and muscle function. Gastroenterol Res Pract 2009: 616054, 2009.
40. Jeppesen PB, Sanguinetti EL, Buchman A, Howard L, Scolapio JS, Ziegler TR, Gregory J, Tappenden KA, Holst J, Mortensen PB. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagonlike peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut 54: 1224-1231, 2005.
41. Jin Q, Esteva FJ. Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer. J Mammary Gland Biol Neoplasia 13: 485-498, 2008.
42. Kato Y, Yu D, Schwartz MZ. Glucagonlike peptide-2 enhances small intestinal absorptive function and mucosal mass in vivo. J Pediatr Surg 34: 18-20; discussion 20-11, 1999.
43. Koehler JA, Harper W, Barnard M, Yusta B, Drucker DJ. Glucagonlike peptide-2 does not modify the growth or survival of murine or human intestinal tumor cells. Cancer Res 68: 7897-7904, 2008.
44. Koehler JA, Yusta B, Drucker DJ. The HeLa cell glucagon-like peptide- 2 receptor is coupled to regulation of apoptosis and ERK1/2 activation through divergent signaling pathways. Mol Endocrinol 19: 459-473, 2005.
45. Lee G, Goretsky T, Managlia E, Dirisina R, Singh AP, Brown JB, May R, Yang GY, Ragheb JW, Evers BM, Weber CR, Turner JR, He XC, Katzman RB, Li L, Barrett TA. Phosphoinositide 3-kinase signaling mediates beta-catenin activation in intestinal epithelial stem and progenitor cells in colitis. Gastroenterology 139: 869-881, 2010.
46. Leen JL, Izzo A, Upadhyay C, Rowland KJ, Dube PE, Gu S, Heximer SP, Rhodes CJ, Storm DR, Lund PK, Brubaker PL. Mechanism of action of glucagon-like peptide-2 to increase IGF-I mRNA in intestinal subepithelial fibroblasts. Endocrinology 152: 436-446, 2011.
47. LeRoith D. Insulin-like growth factor I receptor signaling- overlapping or redundant pathways? Endocrinology 141: 1287-1288, 2000.
48. Liu X, Murali SG, Holst JJ, Ney DM. Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association withincreased insulin-like growth factor-I responses in rats. Am J Physiol Regul Integr Comp Physiol 295: R1794-R1802, 2008.
49. Lund PK. IGFs and the digestive tract. In: The IGF System: Molecular Biology, Physiology, and Clinical Applications, edited by Roberts CT and Rosenfeld RG. Totowa, NJ: Humana, 1999, p. 517-544.
50. Luo F, Brooks DG, Ye H, Hamoudi R, Poulogiannis G, Patek CE, Winton DJ, Arends MJ. Mutated K-ras(Asp12) promotes tumourigenesis in Apc(Min) mice more in the large than the small intestines, with synergistic effects between K-ras and Wnt pathways. Int J Exp Pathol 90: 558-574, 2009.
51. MacDonald RS. The role of insulin-like growth factors in small intestinal cell growth and development. Horm Metab Res 31: 103-113, 1999.
52. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med 361: 2449-2460, 2009.
53. Munroe DG, Gupta AK, Kooshesh F, Vyas TB, Rizkalla G, Wang H, Demchyshyn L, Yang ZJ, Kamboj RK, Chen H, McCallum K, Sumner-Smith M, Drucker DJ, Crivici A. Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2. Proc Natl Acad Sci USA 96: 1569-1573, 1999.
54. Nelson DW, Murali SG, Liu X, Koopmann MC, Holst JJ, Ney DM. Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats. Am J Physiol Regul Integr Comp Physiol 294: R1175-R1184, 2008.
55. Ohneda K, Ulshen MH, Fuller CR, D'Ercole AJ, Lund PK. Enhanced growth of small bowel in transgenic mice expressing human insulin-like growth factor I. Gastroenterology 112: 444-454, 1997.
56. Orskov C, Hartmann B, Poulsen SS, Thulesen J, Hare KJ, Holst JJ. GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors. Regul Pept 124: 105-112, 2005.
57. Qiu W, Leibowitz B, Zhang L, Yu J. Growth factors protect intestinal stem cells from radiation-induced apoptosis by suppressing PUMA through the PI3K/AKT/p53 axis. Oncogene 29: 1622-1632.
58. Roudabush FL, Pierce KL, Maudsley S, Khan KD, Luttrell LM. Transactivation of the EGF receptor mediates IGF-1-stimulated shc phosphorylation and ERK1/2 activation in COS-7 cells. J Biol Chem 275: 22583-22589, 2000.
59. Rowland KJ, Trivedi S, Brubaker PL. The intestinal epithelial insulinlike growth factor-1 receptor is required for acute intestinal adaptive growth effects but not activation of canonical Wnt signaling by glucagonlike peptide-2 (Abstract). Gastroenterology 136, Suppl 1: A-133, 2009.
60. Sanderson IR, Naik S. Dietary regulation of intestinal gene expression. Annu Rev Nutr 20: 311-338, 2000.
61. Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469: 415-418, 2011.
62. Sheng H, Shao J, Townsend CM Jr, Evers BM. Phosphatidylinositol 3-kinase mediates proliferative signals in intestinal epithelial cells. Gut 52: 1472-1478, 2003.
63. Shin ED, Estall JL, Izzo A, Drucker DJ, Brubaker PL. Mucosal adaptation to enteral nutrients is dependent on the physiologic actions of glucagon-like peptide-2 in mice. Gastroenterology 128: 1340-1353, 2005.
64. Sigalet DL, Wallace LE, Holst JJ, Martin GR, Kaji T, Tanaka H, Sharkey KA. Enteric neural pathways mediate the anti-inflammatory actions of glucagon-like peptide 2. Am J Physiol Gastrointest Liver Physiol 293: G211-G221, 2007.
65. Sokolovic M, Wehkamp D, Sokolovic A, Vermeulen J, Gilhuijs-Pederson LA, van Haaften RI, Nikolsky Y, Evelo CT, van Kampen AH, Hakvoort TB, Lamers WH. Fasting induces a biphasic adaptive metabolic response in murine small intestine. BMC Genomics 8: 361, 2007.
66. Stevens FM, Flanagan RW, O'Gorman D, Buchanan KD. Glucagonoma syndrome demonstrating giant duodenal villi. Gut 25: 784-791, 1984.
67. Tavares W, Drucker DJ, Brubaker PL. Enzymatic- and renal-dependent catabolism of the intestinotropic hormone glucagon-like peptide-2 in rats. Am J Physiol Endocrinol Metab 278: E134-E139, 2000.
68. Theiss AL, Simmons JG, Jobin C, Lund PK. Tumor necosis factor (TNF) alpha increases collagen accumulation and proliferation in intestinal myofibroblasts via TNF receptior 2. J Biol Chem 280: 6099-6109, 2005.
69. Thulesen J, Hartmann B, Hare KJ, Kissow H, Orskov C, Holst JJ, Poulsen SS. Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice. Gut 53: 1145-1150, 2004
70. Thulesen J, Knudsen LB, Hartmann B, Hastrup S, Kissow H, Jeppesen PB, Orskov C, Holst JJ, Poulsen SS. The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. Regul Pept 103: 9-15, 2002.
71. Tsai CH, Hill M, Drucker DJ. Biological determinants of intestinotrophic properties of GLP-2 in vivo. Am J Physiol Gastrointest Liver Physiol 272: G662-G668, 1997.
72. Walsh NA, Yusta B, DaCambra MP, Anini Y, Drucker DJ, Brubaker PL. Glucagon-like peptide-2 receptor activation in the rat intestinal mucosa. Endocrinology 144: 4385-4392, 2003.
73. Washizawa N, Gu LH, Gu L, Openo KP, Jones DP, Ziegler TR. Comparative effects of glucagon-like peptide-2 (GLP-2), growth hormone (GH), and keratinocyte growth factor (KGF) on markers of gut adaptation after massive small bowel resection in rats. JPEN J Parenter Enteral Nutr 28: 399-409, 2004.
74. Xiao Q, Boushey RP, Drucker DJ, Brubaker PL. Secretion of the intestinotropic hormone glucagon-like peptide 2 is differentially regulated by nutrients in humans. Gastroenterology 117: 99-105, 1999.
75. Yakar S, Pennisi P, Wu Y, Zhao H, LeRoith D. Clinical relevance of systemic and local IGF-I. Endocr Dev 9: 11-16, 2005.
76. Yusta B, Estall J, Drucker DJ. 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 277: 24896 -24906, 2002.
77. Yusta B, Holland D, Koehler JA, Maziarz M, Estall JL, Higgins R, Drucker DJ. ErbB signaling is required for the proliferative actions of GLP-2 in the murine gut. Gastroenterology 137: 986-996, 2009.
78. Yusta B, Huang L, Munroe D, Wolff G, Fantaske R, Sharma S, Demchyshyn L, Asa SL, Drucker DJ. Enteroendocrine localization of GLP-2 receptor expression in humans and rodents. Gastroenterology 119: 744-755, 2000.
79. Yusta B, Somwar R, Wang F, Munroe D, Grinstein S, Klip A, Drucker DJ. 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: 30459-30467, 1999.