Metabolic and Digestive Functions of Glucagon-Like Peptide-1 in Pigs

Ľubomír Čulka; Zuzana Krepelková; Katarína Bárdová; Jaroslav Novotný

doi:10.2478/fv-2026-0018

.blurhash-client-img { display: none !important; }

Metabolic and Digestive Functions of Glucagon-Like Peptide-1 in Pigs

Folia Veterinaria

Volume 70 (2026): Issue 2 (June 2026)

By: Ľubomír Čulka, Zuzana Krepelková, Katarína Bárdová and Jaroslav Novotný

Open Access

|Jun 2026

Abstract

Glucagon-like peptide-1 (GLP-1) is a hormone with multiple biological effects that plays a key role in glucose metabolism, digestion, and energy homeostasis. In pigs, GLP-1 serves as an important metabolic regulator with relevance for both production efficiency and translational research. This review summarizes current knowledge on GLP-1 physiology in pigs, including synthesis, secretion, metabolism, and biological actions. Particular emphasis is placed on the role of GLP-1 in insulin secretion, digestive function, including gastric mucosal protection and ulcer prevention, appetite regulation, and lipid metabolism. Understanding GLP-1 mechanisms in pigs has practical implications for optimizing feeding strategies in swine production and provides insights relevant to human metabolic disease research.

References

1. Holst, J. J., 2007: The physiology of glucagon-like peptide-1. Physiol. Rev., 87, 4, 1409–1439. DOI: 10.1152/physrev.00034.2006
Search in Google Scholar Back to article
2. Müller, T. D., Finan B., Bloom, S. R., D´Alessio, D., Drucker, D. J., Flatt, P. R., et al., 2019: Glucagon-like peptide 1 (GLP-1). Mol. Metab., 30, 72–130. DOI: 10.1016/j. molmet.2019.09.010
Search in Google Scholar Back to article
3. Smits, M. M., van Raalte, D. H., Tonneijck, L., Muskiet, M. H., Kramer, M. H., Cahen, D. L., 2016: GLP-1 based therapies: clinical implications for gastroenterologists. Gut, 65, 702–711. DOI: 10.1136/gutjnl-2015-310572
Search in Google Scholar Back to article
4. Spurlock, M. E., Gabler, N. K., 2008: The development of porcine models of obesity and the metabolic syndrome. J. Nutr., 138, 2, 397–402. DOI: 10.1093/jn/138.2.397
Search in Google Scholar Back to article
5. Koopmans, S. J., Mroz, Z., Dekker, R., Corbijn, H., Ackermans, M., Sauerwein, H., 2006: Association of insulin resistance with hyperglycemia in streptozotocin-diabetic pigs: effects of metformin at isoenergetic feeding in a type 2-like diabetic pig model. Metabolism, 55, 7, 960–971. DOI: 10.1016/j.metabol.2006.03.004
Search in Google Scholar Back to article
6. Renner, S., Blutke, A., Clauss, S., Deeg, C. A., Kemter, E., Merkus, D., et al., 2020: Porcine models for studying complications and organ crosstalk in diabetes mellitus. Cell Tissue Res., 380, 341–378. DOI: 10.1007/s00441-019-03158-9
Search in Google Scholar Back to article
7. Baggio, L. L., Drucker, D. J., 2007: Biology of incretins: GLP-1 and GIP. Gastroenterology, 132, 6, 2131–2157. DOI: 10.1053/j.gastro.2007.03.054
Search in Google Scholar Back to article
8. Eissele, R., Göke, R., Willemer, S., Harthus, H. P., Vermeer, H., Arnold, R., et al., 1992: Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur. J. Clin. Invest., 22, 4, 283–291. DOI: 10.1111/j.1365-2362.1992.tb01464.x
Search in Google Scholar Back to article
9. Deacon, C. F., Pridal, L., Klarskov, L., Olesen, M., Holst, J. J., 1996: Glucagon-like peptide-1 undergoes differential tissue-specific metabolism in the anesthetized pig. Am. J. Physiol. Endocrinol. Metab. .271, 3, E458–E464. DOI: 10.1152/ajpendo.1996.271.3.E458
Search in Google Scholar Back to article
10. Hansen, L., Deacon, C. F., Orskov, C., Holst, J. J., 1999: Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology, 140, 11, 5356–5363. DOI: 10.1210/endo.140.11.7143
Search in Google Scholar Back to article
11. Deacon, C. F., Hughes, T. E., Holst, J. J., 1998: Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig. Diabetes, 47, 5, 764–769. DOI: 10.2337/diabetes.47.5.764
Search in Google Scholar Back to article
12. Hansen, C. F., Thymann, T., Andersen, A. D., Holst, J. J., Hartmann, B., Hilsted, L., et al., 2016: Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs. Am. J. Physiol. Gastrointest. Liver Physiol., 310, 8, G550–G560. DOI: 10.1152/ajpgi.00221.2015
Search in Google Scholar Back to article
13. Hansen, L., Hartmann, B., Mineo, H., Holst, J. J., 2004: Glucagon-like peptide-1 secretion is influenced by perfu-sate glucose concentration and by a feedback mechanism involving somatostatin in isolated perfused porcine ileum. Regul. Pept., 118, 1–2, 11–18. DOI: 10.1016/j.regpep.2003.10.021
Search in Google Scholar Back to article
14. Hirasawa, A., Tsumaya, K., Awaji, T., Katsuma, S., Adachi, T., Yamada, M., et al., 2005: Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat. Med., 11, 1, 90–94. DOI: 10.1038/nm1168
Search in Google Scholar Back to article
15. Li, Z., Yi, C. X., Katiraei, S., Kooijman, S., Zhou, E., Chung, C. K., et al., 2018: Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit. Gut, 67, 1269–1279. DOI: 10.1136/gutjnl-2017-314050
Search in Google Scholar Back to article
16. Hansen, L., Lampert, S., Mineo, H., Holst, J. J., 2004: Neural regulation of glucagon-like peptide-1 secretion in pigs. Am. J. Physiol. Endocrinol. Metab., 287, 5, E939–E947. DOI: 10.1152/ajpendo.00197.2004
Search in Google Scholar Back to article
17. Liu, C., Liu, Y., Xin, Y., Wang, Y., 2022: Circadian secretion rhythm of GLP-1 and its influencing factors. Front. Endocrinol. (Lausanne), 13, 991397. DOI: 10.3389/fendo.2022.991397
Search in Google Scholar Back to article
18. Simonsen, L., Holst, J. J., Deacon, C. F., 2006: Exendin-4, but not glucagon-like peptide-1, is cleared exclusively by glomerular filtration in anaesthetised pigs. Diabetologia, 49, 706–712. DOI: 10.1007/s00125-005-0128-9
Search in Google Scholar Back to article
19. Kreymann, B., Ghatei, M. A., Williams, G., Bloom, S. R., 1987: Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet, 330, 8571, 1300–1304. DOI: 10.1016/S0140-6736(87)91194-9
Search in Google Scholar Back to article
20. Nauck, M. A., Quast, D. R., Wefers, J., Pfeiffer, A. F. H., 2021: The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update. Diabetes Obes. Metab., 23 (Suppl. 3), 5–29. DOI: 10.1111/dom.14496
Search in Google Scholar Back to article
21. Nauck, M. A., Heimesaat, M. M., Orskov, C., Holst, J. J., Ebert, R., Creutzfeldt, W., 1993: Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J. Clin. Invest., 91, 301–307. DOI: 10.1172/JCI116186
Search in Google Scholar Back to article
22. Drucker, D. J., 2006: The biology of incretin hormones. Cell Metab., 3, 3, 153–165. DOI: 10.1016/j.cmet.2006.01.004
Search in Google Scholar Back to article
23. Seino, S., Sugawara, K., Yokoi, N., Takahashi, H., 2017: β-Cell signalling and insulin secretagogues: A path for improved diabetes therapy. Diabetes Obes. Metab., 19 (Suppl. 1), 22–29. DOI: 10.1111/dom.12995
Search in Google Scholar Back to article
24. Pedersen, J., Ugleholdt, R. K., Jørgensen, S. M., Windeløv, J. A., Grunddal, K. V., Schwartz, T. W, et al., 2013: Glucose metabolism is altered after loss of L cells and α-cells but not influenced by loss of K cells. Am. J. Physiol. Endocrinol. Metab., 304, 1, E60–E73. DOI: 10.1152/ajpendo.00547.2011
Search in Google Scholar Back to article
25. Trahair, J. F., Sangild, P. T., 1997: Systemic and luminal influences on the perinatal development of the gut. Equine Vet. J., Suppl., 24, 40–50. DOI: 10.1111/j.2042-3306.1997. tb05077.x
Search in Google Scholar Back to article
26. Schirra, J., Göke, B., 2005: The physiological role of GLP-1 in human: incretin, ileal brake or more? Regul. Pept., 128, 2, 109–115. DOI: 10.1016/j.regpep.2004.06.018
Search in Google Scholar Back to article
27. Ranganath, L. R., Beety, J. M., Morgan, L. M., Wright, J. W., Howland, R., Marks, V., 1996: Attenuated GLP-1 secretion in obesity: cause or consequence? Gut, 38, 916–919. DOI: 10.1136/gut.38.6.916
Search in Google Scholar Back to article
28. Vrang, N., Larsen, P. J., 2010: Preproglucagon derived peptides GLP-1, GLP-2 and oxyntomodulin in the CNS: role of peripherally secreted and centrally produced peptides. Prog. Neurobiol., 92, 3, 442–462. DOI: 10.1016/j.pneurobio.2010.07.003
Search in Google Scholar Back to article
29. Nauck, M. A., Meier, J. J., 2018: Incretin hormones: Their role in health and disease. Diabetes Obes. Metab., 20 (Suppl. 1), 5–21. DOI: 10.1111/dom.13129
Search in Google Scholar Back to article
30. Moeser, A. J., Pohl, C. S., Rajput, M., 2017: Weaning stress and gastrointestinal barrier development: Implications for lifelong gut health in pigs. Anim. Nutr., 3, 4, 313–321. DOI: 10.1016/j.aninu.2017.06.003
Search in Google Scholar Back to article
31. Krepelková, Z., Novotný, J., Bárdová, K., Link, R., Csörgö, A., 2024: Gastric ulcers in pigs – a review. Folia Vet., 68, 2, 33–42. DOI: 10.2478/fv-2024-0015
Search in Google Scholar Back to article
32. Lee, Y. S., Jun, H. S., 2016: Anti-inflammatory effects of GLP-1-based therapies beyond glucose control. Mediators Inflamm., 2016, 3094642. DOI: 10.1155/2016/3094642
Search in Google Scholar Back to article
33. Wong, C. K., Drucker, D. J., 2025: Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits. J. Clin. Invest., 135, 21, e194751. DOI: 10.1172/jci194751
Search in Google Scholar Back to article
34. Sheikh, A., 2013: Direct cardiovascular effects of glucagon like peptide-1. Diabetol. Metab. Syndr., 5, 47. DOI: 10.1186/1758-5996-5-47
Search in Google Scholar Back to article
35. Delgado-Aros, S., Kim, D. Y., Burton, D. D., Thomforde, G. M., Stephens, D., Brinkmann, B. H., et al., 2002: Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am. J. Physiol. Gastrointest. Liver Physiol., 282, 3, G424–G431. DOI: 10.1152/ajpgi.2002.282.3.G424
Search in Google Scholar Back to article
36. Wettergren, A., Wøjdemann, M., Holst, J. J., 1998: Glucagon-like peptide-1 inhibits gastropancreatic function by inhibiting central parasympathetic outflow. Am. J. Physiol. Gastrointest. Liver Physiol., 275, 5, G984–G992. DOI: 10.1152/ajpgi.1998.275.5.G984
Search in Google Scholar Back to article
37. Andrews, C. N., Bharucha, A. E., Camilleri, M., Low, P. A., Seide, B., Burton, D., et al., 2007: Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults. Am. J. Physiol. Gastrointest. Liver Physiol., 292, 5, G1359–1365. DOI: 10.1152/ajpgi.00403.2006
Search in Google Scholar Back to article
38. Holst, J. J., Andersen, D. B., Grunddal, K. V., 2022: Actions of glucagon-like peptide-1 receptor ligands in the gut. Br. J. Pharmacol., 179, 4, 727–742. DOI: 10.1111/bph.15611
Search in Google Scholar Back to article
39. Colwill, M., Povlsen, S., Pollok, R., Patel, K., Goodhand, J., Ahmad, T., et al., 2025: Glucagon-like peptide-1 (GLP-1) receptor agonists in inflammatory bowel disease: mechanisms, clinical implications, and therapeutic potential. J. Crohns Colitis, 19, 9, jjaf167. DOI: 10.1093/ecco-jcc/jjaf167
Search in Google Scholar Back to article
40. Tang-Christensen, M., Vrang, N., Larsen, P. J., 1998: Glucagon-like peptide 1(7-36) amide’s central inhibition of feeding and peripheral inhibition of drinking are abolished by neonatal monosodium glutamate treatment. Diabetes, 47, 4, 530–537. DOI: 10.2337/diabetes.47.4.530
Search in Google Scholar Back to article
41. Lee, J., Hong, S. W., Rhee, E. J., Lee, W. Y., 2012: GLP-1 receptor agonist and non-alcoholic fatty liver disease. Diabetes Metab. J., 36, 4, 262–267. DOI: 10.4093/dmj.2012.36.4.262
Search in Google Scholar Back to article
42. Villanueva-Peñacarrillo, M. L., Márquez, L., González, N., Díaz-Miguel, M., Valverde, I., 2001: Effect of GLP-1 on lipid metabolism in human adipocytes. Horm. Metab. Res., 33, 2, 73–77. DOI: 10.1055/s-2001-12428
Search in Google Scholar Back to article
43. Theodorakis, M. J., Carlson, O., Michopoulos, S., Doyle, M. E., Juhaszova, M., Petraki, K., et al., 2006: Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am. J. Physiol. Endocrinol. Metab., 290, 3, E550–E559. DOI: 10.1152/ajpendo.00326.2004
Search in Google Scholar Back to article
44. Yoder, S. M., Yang, Q., Kindel, T. L., Tso, P., 2010: Differential responses of the incretin hormones GIP and GLP-1 to increasing doses of dietary carbohydrate but not dietary protein in lean rats. Am. J. Physiol. Gastrointest. Liver Physiol., 299, 2, G476–G485. DOI: 10.1152/ajpgi.00432.2009
Search in Google Scholar Back to article
45. Deacon, C. F., 2019: Physiology and pharmacology of DPP-4 in glucose homeostasis and the ttreatment of type 2 diabetes. Front. Endocrinol. (Lausanne), 10, 80. DOI: 10.3389/fendo.2019.00080
Search in Google Scholar Back to article
46. Alturki, M. S., Alkhodier, R. A., Gomaa, M. S., Hussein, D. A., Tawfeeq, N., Al Khzem, A. H., et al., 2025: Structure-based discovery of orthosteric non-peptide GLP-1R agonists via integrated virtual screening and molecular dynamics. Int. J. Mol. Sci., 26, 13, 6131. DOI: 10.3390/ijms26136131
Search in Google Scholar Back to article