Skip to main content
×
×
Home

PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS

  • K. K. Qi (a1), J. Wu (a1), B. Deng (a1), Y. M. Li (a1) and Z. W. Xu (a1)...
Abstract

This study was conducted to determine the effects on intestinal function, anti-inflammatory role and possible mechanism of polyethylene glycosylated (PEGylated) porcine glucagon-like peptide-2 (pGLP-2), a long-acting form of pGLP-2, in weaning piglets challenged with Escherichia coli lipopolysaccharide (LPS). We divided 18 weaned piglets on day 21 into three groups (control, LPS and LPS+PEG-pGLP-2; n=6). The piglets from the LPS+PEG-pGLP-2 group were injected with PEG-pGLP-2 at 10 nmol/kg BW from 5 to 7 days of the trials daily. On 8th day, the piglets in the LPS and LPS+PEG-pGLP-2 groups were intraperitoneally administered with 100 µg LPS/kg. The control group was administered with the same volume of saline solution. The piglets were then sacrificed on day 28. Afterwards, serum, duodenum, jejunum and ileum samples were collected for analysis of structural and functional endpoints. LPS+PEG-pGLP-2 treatment increased (P<0.05) lactase activities in the duodenum and the jejunum compared with LPS treatment. LPS+PEG-pGLP-2 treatment also significantly increased sucrase activity in the jejunum compared with LPS treatment. Furthermore, LPS treatment increased (P<0.05) the mRNA expression levels of interleukin (IL)-8, tumour necrosis factor-α (TNF-α) and IL-10 in the ileum compared with the control treatment. By contrast, LPS+PEG-pGLP-2 treatment decreased (P<0.05) the mRNA expression levels of IL-8, IL-10 and TNF-α in the ileum compared with the LPS treatment. LPS treatment also increased (P<0.05) the mRNA expression level of GLP-2 receptor (GLP-2R) and the percentage of GLP-2R-positive cells in the ileum; by comparison, these results were (P<0.05) reduced by LPS+PEG-pGLP-2 treatment. Moreover, LPS+PEG-pGLP-2 treatment increased (P<0.05) the content of serum keratinocyte growth factor compared with the control group and the LPS group. The protective effects of PEG-pGLP-2 on intestinal digestive function were associated with the release of GLP-2R mediator (keratinocyte growth factor) and the decrease in the expressions of intestinal pro-inflammatory cytokines.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS
      Available formats
      ×
Copyright
Corresponding author
E-mail: zjsnkyxzw@163.com
References
Hide All
Au, A, Gupta, A, Schembri, P and Cheeseman, CI 2002. Rapid insertion of GLUT2 into the rat jejunal brush-border membrane promoted by glucagon-like peptide 2. Biochemical Journal 367, 247254.
Baldassano, S, Amato, A, Cappello, F, Rappa, F and Mulè, F 2013. Glucagon-like peptide-2 and mouse intestinal adaptation to a high-fat diet. Journal of Endocrinology 217, 1120.
Benight, NM, Stoll, B, Olutoye, OO, Holst, JJ and Burrin, DG 2013. GLP-2 delays but does not prevent the onset of necrotizing enterocolitis in preterm pigs. Journal of Pediatric Gastroenterology and Nutrition 56, 623630.
Benjamin, MA, McKay, DM, Yang, PC, Cameron, H and Perdue, M 2000. Glucagon-like peptide-2 enhances intestinal epithelial barrier function of both transcellular and paracellular pathways in the mouse. Gut 47, 112119.
Boushey, RP, Yusta, B and Drucker, DJ 1999. Glucagon-like peptide 2 decreases mortality and reduces the severity of indomethacin-induced murine enteritis. American Journal of Physiology. Endocrinology and Metabolism 277, E937E947.
Brubaker, PL, Izzo, A, Hill, M and Drucker, DJ 1997. Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. American Journal of Physiology. Endocrinology and Metabolism 272, E1050E1058.
Burrin, DG, Stoll, B, Guan, XF, Cui, LW, Chang, XY and Hadsell, D 2007. GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets. American Journal of Physiology. Endocrinology and Metabolism 292, E281E291.
Burrin, DG, Stoll, B, Jiang, R, Petersen, Y, Elnif, J, Buddington, RK, Schmidt, M, Holst, JJ, Hartmann, B and Sangild, PT 2000. GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis. American Journal of Physiology. Gastrointestinal and Liver Physiology 279, G1249G1256.
Canesi, L, Malatesta, M, Battistelli, S, Ciacci, C, Gallo, G and Gazzanelli, G 2000. Immunoelectron microscope analysis of epidermal growth factor receptor (KGFR) in isolated Mytilus galloprovincialis (Lam.) digestive gland cells: evidence for ligand-induced changes in KGFR intracellular distribution. Journal of Experimental Zoology 286, 690698.
DaCambra, MP, Yusta, B, Sumner-Smith, M, Crivici, A, Drucker, DJ and Brubaker, PL 2000. Structural determinants for activity of glucagon-like peptide-2. Biochemistry 39, 88888894.
Drucker, DJ and Yusta, B 2014. Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annual Review of Physiology 76, 561583.
Drucker, DJ, Erlich, P, Asa, SL and Brubaker, PL 1996. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proceedings of the National Academy of Sciences of the United States of America 93, 79117916.
Drucker, DJ, Yusta, B, Boushey, RP, DeForest, L and Brubaker, PL 1999. Human [Gly2] GLP-2 reduces the severity of colonic injury in a murine model of experimental colitis. American Journal of Physiology. Gastrointestinal and Liver Physiology 276, G79G91.
Kaji, T, Tanaka, H, Redstone, H, Wallace, LE, Holst, JJ and Sigalet, DL 2009. Temporal changes in the intestinal growth promoting effects of glucagon-like peptide 2 following intestinal resection. Journal of Surgical Research 152, 271280.
Kitchen, PA, Fitzgerald, AJ, Goodlad, RA, Barley, NF, Ghatei, MA, Legon, S, Bloom, SR, Price, A, Walters, JR and Forbes, A 2000. Glucagon-like peptide-2 increases sucrase-isomaltase but not caudal-related homeobox protein-2 gene expression. American Journal of Physiology. Gastrointestinal and Liver Physiology 278, G425G428.
Lallès, JP, Boudry, G, Favier, C, Floc’h, NL, Luron, I, Montagne, L, Oswald, IP, Pié, S, Piel, C and Sève, B 2004. Gut function and dysfunction in young pigs: physiology. Animal Research 53, 301316.
Lovshin, J, Yusta, B, Iliopoulos, I, Migirdicyan, A, Dableh, L, Brubaker, PL and Drucker, DJ 2000. Ontogeny of the glucagon-like peptide-2 receptor axis in the developing rat intestine. Endocrinology 141, 41944201.
Mercer, DW, Smith, GS, Cross, JM, Russell, DH, Chang, L and Cacioppo, J 1996. Effects of lipopolysaccharide on intestinal injury: potential role of nitric oxide and lipid peroxidation. Journal of Surgical Research 63, 185192.
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 and Crivici, A 1999. Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2. Proceedings of the National Academy of Sciences of the United States of America 96, 15691573.
Ørskov, C, Hartmann, B, Poulsen, SS, Thulesen, J, Hare, KJ and Holst, JJ 2005. GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors. Regulatory Peptides 124, 105112.
Pedersen, NB, Hjollund, KR, Johnsen, AH, Orskov, C, Rosenkilde, MM, Hartmann, B and Holst, JJ 2008. Porcine glucagon-like peptide-2: structure, signaling, metabolism and effects. Regulatory Peptides 146, 310320.
Pereira-Fantini, PM, Nagy, ES, Thomas, SL, Taylor, RG, Sourial, M, Paris, MC, Holst, JJ, Fuller, PJ and Bines, JE 2008. GLP-2 administration results in increased proliferation but paradoxically an adverse outcome in a juvenile piglet model of short bowel syndrome. Journal of Pediatric Gastroenterology and Nutrition 46, 2028.
Petersen, YM, Burrin, DG and Sangild, PT 2001. GLP-2 has differential effects on small intestine growth and function in fetal and neonatal pigs. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 281, R1986R1993.
Petersen, YM, Elnif, J, Schmidt, M and Sangild, PT 2002. Glucagon-like peptide 2 enhances maltase-glucoamylase and sucrase-isomaltase gene expression and activity in parenterally fed premature neonatal piglets. Pediatric Research 52, 498503.
Petersen, YM, Hartmann, B, Schmidt, MH, Holst, JJ and Sangild, PT 2000. Exogenous glucagon-like peptide 2 has a limited effect on mucosal growth and enzyme activity in the fetus when compared to the neonate. Gastroenterology 118, A561.
Petersen, YM, Hartmann, B, Holst, JJ, Le Huerou-Luron, I, Bjørnvad, CR and Sangild, PT 2003. Introduction of enteral food increases plasma GLP-2 and decreases GLP-2 receptor mRNA abundance during pig development. Journal of Nutrition 133, 17811786.
Pi, DG, Liu, YL, Shi, HF, Li, S, Odle, J, Lin, X, Zhu, HL, Chen, F, Hou, YQ and Leng, WB 2014. Dietary supplementation of aspartate enhances intestinal integrity and energy status in weaning piglets after lipopolysaccharide challenge. Journal of Nutritional Biochemistry 25, 456462.
Pié, S, Lallès, JP, Blazy, F, Laffitte, J, Sève, B and Oswald, IP 2004. Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets. Journal of Nutrition 134, 641647.
Qi, KK, Wu, J, Wan, J, Men, XM and Xu, ZW 2014. Purified PEGylated porcine glucagon-like peptide-2 reduces the severity of colonic injury in a murine model of experimental colitis. Peptides 52, 1118.
Sigalet, DL, Wallace, LE, Holst, JJ, Martin, GR, Kaji, T, Tanaka, H and Sharkey, KA 2007. Enteric neural pathways mediate the anti-inflammatory actions of glucagon-like peptide 2. American Journal of Physiology. Gastrointestinal and Liver Physiology 293, G211G221.
Sigalet, DL, de Heuvel, E, Wallace, L, Bulloch, E, Turner, J, Wales, PW, Nation, P, Wizzard, PR, Hartmann, B, Assad, M and Holst, JJ 2014. Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs. Regulatory Peptides 188, 7080.
Thymann, T, Stoll, B, Mecklenburg, L, Burrin, DG, Vegge, A, Qvist, N, Eriksen, T, Jeppesen, PB and Sangild, PT 2014a. Acute effects of the glucagon-like peptide 2 analogue, teduglutide, on intestinal adaptation in newborn pigs with short bowel syndrome. Journal of Pediatric Gastroenterology and Nutrition 58, 694702.
Thymann, T, Le Huërou-Luron, I, Petersen, YM, Hedemann, MS, Elinf, J, Jensen, BB, Holst, JJ, Hartmann, B and Sangild, PT 2014b. Glucagon-like peptide 2 (GLP-2) treatment improves intestinal adaptation during weaning. Journal of Animal Science 92, 20702079.
Touchette, KJ, Carroll, JA, Allee, GL, Matteri, RL, Dyer, CJ, Beausang, LA and Zannelli, ME 2002. Effect of spray-dried plasma and lipopolysaccharide exposure on weaned pigs: I. Effects on the immune axis of weaned pigs. Journal of Animal Science 80, 494501.
Tsai, CH, Hill, M, Asa, SL, Brubaker, PL and Drucker, DJ 1997. Intestinal growth-promoting properties of glucagon-like peptide 2 in mice. American Journal of Physiology. Endocrinology and Metabolism 36, E77E84.
Wang, QJ, Hou, YQ, Yi, D, Wang, L, Ding, BY, Chen, X, Long, MH, Liu, YL and Wu, GY 2013. Protective effects of N-acetylcysteine on acetic acid-induced colitis in a porcine model. BMC Gastroenterology 13, 133.
Wojdemann, M, Wettergren, A, Hartmann, B, Hilsted, L and Holst, JJ 1999. Inhibition of sham feeding-stimulated human gastric acid secretion by glucagon-like peptide 2. Journal of Clinical Endocrinology and Metabolism 84, 25132517.
Yi, GF, Carroll, JA, Allee, GL, Gaines, AM, Kendall, DC, Usry, JL, Toride, Y and Izuru, S 2005. Effect of glutamine and spray-dried plasma on growth performance, small intestinal morphology, and immune responses of Escherichia coli K88-challenged weaned pigs. Journal of Animal Science 83, 634643.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

animal
  • ISSN: 1751-7311
  • EISSN: 1751-732X
  • URL: /core/journals/animal
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Full text views

Total number of HTML views: 25
Total number of PDF views: 177 *
Loading metrics...

Abstract views

Total abstract views: 333 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 13th June 2018. This data will be updated every 24 hours.