胰高血糖素样肽-2及其在畜牧生产中的应用

doi:10.16431/j.cnki.1671-7236.2019.06.006

摘要/Abstract

摘要：

胰高血糖素样肽-2（GLP-2）是一条由33个氨基酸残基组成的短肽，主要由位于小肠的边缘和结肠中的L内分泌细胞分泌，与其受体（GLP-2R）结合激活一系列下游的反应来实现其功能。GLP-2具有促进肠道生长发育，修复受损伤肠道，加快营养物质转运与吸收，增强肠黏膜屏障功能等生理作用，目前GLP-2及GLP-2类似物（[Gly-2]GLP-2）已被批准用于治疗短肠综合征等人类肠黏膜损伤性疾病。此外，由于GLP-2功能具有多样性，在畜牧生产上也有广阔的应用前景。如GLP-2可以用于家畜常见的一些肠胃炎的治疗，可用来缓解牛败血症引起的肺脏损伤，在维持肝脏健康方面也可发挥重要作用，还可作为一种厌食信号肽来增加食物在家畜中的转化率，以及用于缓解周围环境改变而引起的家畜不良应激反应，如热应激、缺水应激、氟中毒、饮食转换期间肠功能受损等问题。作者就GLP-2的最新研究进展及其在畜牧生产中的应用进行阐述。

关键词: GLP-2; 研究进展; 应用; 畜牧生产

Abstract:

Glucagon-like peptide-2(GLP-2) is a short peptide consisting of 33 amino acid residues and mainly secreted by L endocrine cells located in the small intestine edge and colon.GLP-2 can binds to its receptor GLP-2R to activate a series of downstream reactions to achieve its functions.It can promote intestinal growth and development,repair of damaged intestine,accelerate nutrient transport and absorption,and enhance intestinal mucosal barrier function.At present,GLP-2 and[Gly-2] GLP-2 have been approved for the treatment of human intestinal mucosal injury diseases such as short bowel syndrome.In addition,GLP-2 has a wide range of applications in livestock production because of its many functions.For example,GLP-2 can be used in the treatment of some common gastrointestinal inflammatory diseases in livestock.It can also alleviate lung injury caused by bovine sepsis and play an important role in maintaining liver health.Besides,as an anorexia signal peptide,GLP-2 can increases the conversion rate of food in livestock.GLP-2 is also used to relieve adverse environmental stress caused by changes in the surrounding environment,such as heat stress,water deficiency stress,fluorosis and intestinal dysfunction during diet switching and so on,In this paper,the latest research progress of GLP-2 and its application in animal production are discussed.

Key words: GLP-2; research progress; application; animal production

中图分类号:

Q514⁺.3

韩斐, 江明锋, 王刚. 胰高血糖素样肽-2及其在畜牧生产中的应用[J]. 《中国畜牧兽医》, 2019, 46(6): 1612-1618.

HAN Fei, JIANG Mingfeng, WANG Gang. Glucagon-like Peptide-2 and Its Application in Animal Production[J]. , 2019, 46(6): 1612-1618.

参考文献

[1] LI F,LU L,PENG Y,et al.Increased GLP2R expression in gastric chief cells of patients with severe obesity regardless of diabetes status[J]. International Journal of Obesity, 2017,41(8):1303.
[2] DRUCKER D J,ERLICH P,ASA S L,et al.Induction of intestinal epithelial proliferation by glucagon-like peptide 2[J].Proceedings of the National Academy of Sciences of the United States of America,1996;93(15):7911-7916.
[3] RING L L,NERUP N,JEPPESEN P B,et al.Glucagon like peptide-2 and neoplasia:A systematic review[J].Expert Review of Gastroenterology & Hepatology, 2017,12(3):1-8.
[4] CONNOR E E,EVOCK-CLOVER C M,WALKER M P,et al.Comparative gut physiology symposium:Comparative physiology of glucagon-like peptide-2:Implications and applications for production and health of ruminants[J].Journal of Animal Science,2015,93(2):492-501.
[5] BURRIN D G,STOLL B,GUAN X.Glucagon-like peptide 2 function in domestic animals[J].Domestic Animal Endocrinology,2003,24(2):103-122.
[6] DRUCKER D J.Biological actions and therapeutic potential of the glucagon-like peptides[J].Gastroenterology,2002,122(2):531-544.
[7] ROCCA A S,BRUBAKER P L.Stereospecific effects of fatty acids on proglucagon-derived peptide secretion in fetal rat intestinal cultures[J].Endocrinology,1995,136(12):5593-5599.
[8] YAMAZAKI K,YASUDA N,INOUE T,et al.The combination of metformin and a dipeptidyl peptidase IV inhibitor prevents 5-fluorouracil-induced reduction of small intestine weight[J].European Journal of Pharmacology,2004,488(1-3):213-218.
[9] MANNUCCI E,TESI F,BARDINI G,et al.Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without type 2 diabetes[J].Journal Diabetes Nutrition and Metabolism,2004,17(6):336-342.
[10] BRUBAKER P L,ANINI Y.Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2[J].Canadian Journal of Physiology and Pharmacology,2003,81(11):1005-1012.
[11] SATO S,HOKARI R,KURIHARA C,et al.Dietary lipids and sweeteners regulate glucagon-like peptide-2 secretion[J].American Journal of Physiology Gastrointestinal & Liver Physiology,2013,304(8):708-714.
[12] SHIRAZI-BEECHEY S P,DALY K,AL-RAMMAHI M,et al.Role of nutrient-sensing taste 1 receptor (T1R) family members in gastrointestinal chemosensing[J].British Journal of Nutrition,2014,111(Suppl 1):8-15.
[13] HANSEN L,HARE K J,HARTMANN B,et al.Metabolism of glucagon-like peptide-2 in pigs:Role of dipeptidyl peptidase Ⅳ[J].Regulatory Peptides,2007,138(2):126-132.
[14] BRUBAKER P L.Glucagon-like peptide-2 and the regulation of intestinal growth and function[J].Comprehensive Physiology,2018,8(3):1185.
[15] TAVARES W,DRUCKER D J,BRUBAKER P L.Enzymatic- and renal dependent catabolism of the intestine otropic hormone glucagonlike peptide-2 in rats[J].American Journal of Physiology-endocrinology and Metabolism,2000,278(1):134-139.
[16] SHIN E D,ESTALL J L,IZZO A,et al.Mucosal adaptation to enteral nutrients is dependent on the physiologic actions of glucagon-like peptide-2 in mice[J].Gastroenterology,2005,128(5):1340-1053.
[17] DRUCKER D J,SHI Q,CRIVICI A,et al.Regulation of the biological activity of glucagon-like peptide 2 by dipeptidyl peptidase Ⅵ[J].Nature Biotechnology,1997,15(7):673-677.
[18] ALTERS S E,MCLAUGHLIN B,SPINK B,et al.GLP2-2G-XTEN:A pharmaceutical protein with improved serum half-life and efficacy in a rat Crohn's disease model[J].PLoS One,2012,7(11):e50630.
[19] PODUST V N,SIM B C,KOTHARI D,et al.Extension of in vivo half-life of biologically active peptides via chemical conjugation to XTEN protein polymer[J].Protein Engineering Design & Selection,2013,26(11):743-753.
[20] QI K K,WU J,DENG B,et al.PEGylated porcine glucagonlike peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS[J].Animal,2015,9(9):1481-1489.
[21] DRUCKER D J,YUSTA B.Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2[J].Annual Review of Physiology,2014,76(76):561-583.
[22] ORSKOV C,HARTMANN B,POULSEN S S,et al.GLP-2 stimulates colonic growth via KGF,released by subepithelial myofibroblasts with GLP-2 receptors[J].Regulatory Peptides,2005,124(1):105-112.
[23] NELSON D W,SHARP J W,BROWNFIELD M S,et al.Localization and activation of glucagon-like peptide-2 receptors on vagal afferents in the rat[J]. Endocrinology,2007,148(5):1954-1962.
[24] LEE S J,LEE J,LI K K,et al.Disruption of the murine Glp2r impairs paneth cell function and increases susceptibility to small bowel enteritis[J].Endocrinology,2012,153(3):1141-1151.
[25] PETERSON L W,ARTIS D.Intestinal epithelial cells:Regulators of barrier function and immune homeostasis[J].Nature Reviews Immunology,2014,14(3):141-153.
[26] CLEVERS H C,BEVINS C L.Paneth cells:Maestros of the small intestinal crypts[J].Annual Review of Physiology,2013,75(1):289-311.
[27] CHEN J,DONG J T,LI X J,et al.Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in obstructive jaundice rats[J].World Journal of Gastroenterology,2015,21:484-490.
[28] HOWARD A,GOODLAD R A,WALTERS J R F,et al.Increased expression of specific intestinal amino acid and peptide transporter mRNA in rats fed by TPN is reversed by GLP-2[J].Journal of Nutrition,2004,134(11):2957.
[29] ORHAN A,GOGENUR I,KISSOW H.The intestinotrophic effects of glucagon-like peptide-2 in relation to intestinal neoplasia[J].The Journal of Clinical Endocrinology & Metabolism,2018,103:2827-2837.
[30] ARDA-PIRINCCIA P,OZTAY F,BAYRAK B B,et al.Teduglutide,a glucagon-like peptide 2 analogue:A novel protective agent with anti-apoptotic and anti-oxidant properties in mice with lung injury[J].Peptides,2012,38(2):238-247.
[31] DRUCKER D J,YUSTA B.Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2[J].Annual Review of Physiology,2014,76(1):561-583.
[32] SORENSEN L B,FLINT A,RABEN A,et al.No effect of physiological concentrations of glucagonlike peptide-2 on appetite and energy intake in normal weight subjects[J]. International Journal of Obesity,2003;27(4):450-456.
[33] JEPPESEN PB,HARTMANN B,THULESEN J,et al.Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon[J].Gastroenterology,2001,120(4):806-815.
[34] IWAI T,JIN K,OHNUKI T,et al.Glucagon-like peptide-2 induced memory improvement and anxiolytic effects in mice[J].Neuropeptides,2015,49:7-14.
[35] SASAKI-HAMADA S,YURI Y,HOSHI M,et al.Immunohistochemical determination of the site of antidepressant-like effects of glucagon-like peptide-2 in ACTH-treated mice[J].Neuroscience,2015,294:156-165.
[36] HADERSLEV K V,JEPPESEN P B,HARTMANN B,et al.Short-term administration of glucagonlike peptide-2:Effects on bone mineral density and markers of bone turnover in short-bowel patients with no colon[J].Gastroenterol, 2002,37(4):392-398.
[37] HENRIKSEN D B,ALEXANDERSEN P,BJARNASON N H,et al.Role of gastrointestinal hormones in postprandial reduction of bone resorption[J].Journal of Bone and Mineral Research,2003,18(12):2180-2189.
[38] HENRIKSEN D B,ALEXANDERSEN P,BYRJALSEN I,et al.Reduction of nocturnal rise in bone resorption by subcutaneous GLP-2[J].Bone,2004,34(1):140-147.
[39] BURRIN D G,STOLL B,GUAN X,et a1.Glucagon-like peptide-2 dose-dependently activates intestinal cell survival and proliferation in neonatal piglets[J].Endocrinology,2005,146(1):22-32.
[40] TAYLOR-EDWARDS C C,BURRIN D G,HOLST J J,et al.Glucagon-like peptide-2(GLP-2) increases small intestinal blood flow and mucosal growth in ruminating calves[J].Journal of Dairy Science,2011,94(2):888-898.
[41] THYMANN T,LE HUROU-LURON I,PETERSEN Y M,et al.Glucagon-like peptide 2 treatment may improve intestinal adaptation during weaning[J]. Journal of Animal Science,2014,92(5):2070-2079.
[42] YU C,JIA G,JIANG Y,et al.Effect of glucagon-like peptide 2 on tight junction in jejunal epithelium of weaned pigs through MAPK signaling pathway[J].Asian-Australasian Journal of Animal Sciences, 2014,27(5):733-742.
[43] QI K K,WU J,XU Z W.Effects of PEGylated porcine glucagon-like peptide-2 therapy in weaning piglets challenged with lipopolysaccharide[J].Peptides,2014,58:7-13.
[44] CONNOR E E,EVOCKCLOVER C M,WALL E H,et al.Glucagon-like peptide 2 and its beneficial effects on gut function and health in production animals[J]. Domestic Animal Endocrinology, 2016,56:56-65.
[45] WALKER M P,EVOCK-CLOVER C M,ELSASSER T H,et al.Short communication:Glucagon-like peptide-2 and coccidiosis alter tight junction gene expression in gastrointestinal tract of dairy calves[J].Dairy Science,2015,98(5):3432-3437.
[46] 汪长城,李雪峰.如何避免畜禽运输应激诱发重大动物疫病[J].当代畜禽养殖业,2013,9:16-17.[KG3] WANG C C,LI X F.How to avoid major animal diseases induced by transportation stress of livestock and poultry[J].Contemporary Livestock and Poultry Breeding, 2013,9:16-17.(in Chinese)
[47] CAMERON H L,PERDUE M H.Stress impairs murine intestinal barrier function:Improvement by glucagon-like peptide-2[J].Journal of Pharmacology & Experimental Therapeutics,2005,314(1):214-220.
[48] 杨柳,刘松财.热应激与畜牧业[J].现代农业科技,2008,22:257.[KG3] YANG L,LIU S C.Heat stress and animal production[J].Modern Agricultural Science and Technology,2008,22:257.(in Chinese)
[49] PIERRE N R,COBANOV B,SCHNITKEY G.Economic losses from heat stress by US livestock industries[J].Journal of Dairy Science,2003,86(5):52-77.
[50] PEARCE S C,VENKATESH M,BODDICKER R L,et al.Heat stress reduces intestinal barrier integrity and favors intestinal glucose transport in growing pigs[J].PLoS One,2013,8(8):e70215.
[51] JEPPESEN P B,HARTMANN B,THULESEN J,et al.Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short bowel patients with colon[J].Gastroenterology,2001,120(4):806-815.
[52] LE HUEROU LURON I,PETERSEN Y M,HARTMANN B,et al.Exogenous GLP-2 has limited effects on weanling-induced intestinal adaptation in piglets[J].Gastroenterology,2002,122(4):A380-A381.
[53] 韩爱云,黄仁录.家禽氟中毒的研究[J].畜禽业,2004,11:18-21.[KG3] HAN A Y,HUANG R L.Study on fluorosis in poultry[J].Livestock and Poultry Industry, 2004,11:18-21.(in Chinese)
[54] SIMON M J,BEIL F T,RVTHER W,et al.High fluoride and low calcium levels in drinking water is associated with low bone mass,reduced bone quality and fragility fractures in sheep[J].Osteoporosis International,2014,25(7):1891-1903.
[55] LENG W,LIU Y,SHI H,et al.Aspartate alleviates injury and regulates mRNA expressions of TLR4 and NOD signaling-related genes in weaned pigs after lipopolysaccharide challenge[J].The Journal of Nutritional Biochemistry,2014,25(6):592-599.
[56] WANG J H,INOUE T,HIGASHIYAMA M,et al.Umami receptor activation increases duodenal bicarbonate secretion via glucagon-like peptide-2 release in rats[J].Journal of Pharmacology and Experimental Therapeutics, 2011,339(2):464-473.
[57] BAUCHART-THEVRET C,STOLL B,BENIGHT N M,et al.Supplementing monosodium glutamate to partia enteral nutrition slows gastric emptying in preterm pigs[J].Journal of Nutrition,2013,143(5):563-570.
[58] SINGH K,RITCHEY J W,CONFER A W.Mannheimia haemolytica:Bacterial-host interactions in bovine pneumonia[J].Veterinary Pathology,2011,48(2):338-348.