Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-08T11:27:13.755Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  12 May 2015

K. K. Qi ,
J. Wu ,
B. Deng ,
Y. M. Li  and
Z. W. Xu
K. K. Qi
Affiliation:
Institute of Animal Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
J. Wu
Affiliation:
Institute of Animal Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
B. Deng
Affiliation:
Institute of Animal Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
Y. M. Li
Affiliation:
Institute of Animal Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
Z. W. Xu*
Affiliation:
Institute of Animal Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
*
†E-mail: [email protected]
Get access

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.

Keywords

PEGylatedporcine glucagon-like peptide-2brush border enzymepro-inflammatory cytokinepiglet
Type
Research Article
Information
animal , Volume 9 , Issue 9 , September 2015 , pp. 1481 - 1489
Copyright
© The Animal Consortium 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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, 247–254.Google Scholar
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, 11–20.CrossRefGoogle ScholarPubMed
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, 623–630.CrossRefGoogle Scholar
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, 112–119.CrossRefGoogle ScholarPubMed
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, E937–E947.Google Scholar
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, E1050–E1058.CrossRefGoogle ScholarPubMed
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, E281–E291.Google Scholar
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, G1249–G1256.Google Scholar
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, 690–698.Google Scholar
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, 8888–8894.Google Scholar
Drucker, DJ and Yusta, B 2014. Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annual Review of Physiology 76, 561–583.CrossRefGoogle ScholarPubMed
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, 7911–7916.CrossRefGoogle ScholarPubMed
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, G79–G91.CrossRefGoogle Scholar
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, 271–280.CrossRefGoogle ScholarPubMed
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, G425–G428.CrossRefGoogle Scholar
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, 301–316.Google Scholar
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, 4194–4201.Google Scholar
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, 185–192.Google Scholar
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, 1569–1573.Google Scholar
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, 105–112.CrossRefGoogle ScholarPubMed
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, 310–320.Google Scholar
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, 20–28.CrossRefGoogle Scholar
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, R1986–R1993.Google Scholar
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, 498–503.Google Scholar
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.Google Scholar
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, 1781–1786.Google Scholar
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, 456–462.Google Scholar
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, 641–647.Google Scholar
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, 11–18.Google Scholar
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, G211–G221.Google Scholar
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, 70–80.Google Scholar
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, 694–702.Google Scholar
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, 2070–2079.Google Scholar
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, 494–501.Google Scholar
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, E77–E84.CrossRefGoogle Scholar
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.Google Scholar
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, 2513–2517.Google Scholar
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, 634–643.Google Scholar