FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Equine Vet J / Expression of the GCG gene and secretion of active glucagon-...
Equine veterinary journal2023; doi: 10.1111/evj.14020

Expression of the GCG gene and secretion of active glucagon-like peptide-1 varies along the length of intestinal tract in horses.

Abstract: Active glucagon-like peptide-1 (aGLP-1) has been implicated in the pathogenesis of equine insulin dysregulation (ID), but its role is unclear. Cleavage of proglucagon (coded by the GCG gene) produces aGLP-1 in enteral L cells. Objective: The aim in vivo was to examine the sequence of the exons of GCG in horses with and without ID, where aGLP-1 was higher in the group with ID. The aims in vitro were to identify and quantify the expression of GCG in the equine intestine (as a marker of L cells) and determine intestinal secretion of aGLP-1. Methods: Genomic studies were case-control studies. Expression and secretion studies in vitro were cross-sectional. Methods: The GCG gene sequence of the exons was determined using a hybridisation capture protocol. Expression and quantification of GCG in samples of stomach duodenum, jejunum, ileum, caecum and ascending and descending colon was achieved with droplet digital PCR. For secretory studies tissue explants were incubated with 12 mM glucose and aGLP-1 secretion was measured with an ELISA. Results: Although the median [IQR] post-prandial aGLP-1 concentrations were higher (p = 0.03) in animals with ID (10.2 [8.79-15.5]), compared with healthy animals (8.47 [6.12-11.7]), there was 100% pairwise identity of the exons of the GCG sequence for the cohort. The mRNA concentrations of GCG and secretion of aGLP-1 differed (p < 0.001) throughout the intestine. Conclusions: Only the exons of the GCG gene were sequenced and breeds were not compared. The horses used for the study in vitro were not assessed for ID and different horses were used for the small, and large, intestinal studies. Conclusions: Differences in post-prandial aGLP-1 concentration were not due to a variant in the exons of the GCG gene sequence in this cohort. Both the large and small intestine are sites of GLP-1 secretion.
© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Get Full Text
Publication Date: 2023-10-18 PubMed ID: 37853957DOI: 10.1111/evj.14020Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the expression and secretion of active glucagon-like peptide-1 (aGLP-1), a diabetes-related hormone, across various sections of the horse intestine. This helps understand the role of aGLP-1 in equine insulin dysregulation. The researchers found no variations in the gene that codes for aGLP-1 between horses with and without insulin dysregulation.

Objective and Methods

  • The research aimed to explore potential variants in the GCG gene, which codes for the hormone aGLP-1 involved in insulin regulation, in horses with and without insulin dysregulation.
  • The researchers also aimed to establish the distribution and quantity of GCG expression, as well as aGLP-1 secretion across various sections of the horse intestine in vitro.
  • The sequence of the exons of GCG gene in horses was determined using a hybridisation capture protocol. This is a molecular technique that helps determine the sequence of specific parts of the genome.
  • Quantification of GCG in samples of stomach duodenum, jejunum, ileum, caecum and colon was achieved using droplet digital PCR, a highly precise method for counting DNA molecules.
  • The researchers also conducted secretory studies, where tissue samples were exposed to glucose to stimulate aGLP-1 secretion, which was then measured using an ELISA.

Results

  • Post-prandial (after mealtime) aGLP-1 concentrations were higher in horses with insulin dysregulation. However, there were no differences found in the exons of the GCG gene sequence between the healthy and insulin dysregulated horses.
  • GCG gene expression and aGLP-1 secretion varied significantly throughout the horse intestine.

Conclusion

  • The researchers concluded that the differences in aGLP-1 concentrations post meals were not due a variant in the exons of the GCG gene sequence.
  • aGLP-1 secretion was observed in both the small and large intestines.
  • The conclusions are limited as only the exons of the GCG gene were sequenced and the breeds of horses were not compared.
  • The same set of horses were not used to study both small and large intestines, and they were not assessed for insulin dysregulation before carrying out the study.

Cite This Article

APA
Fitzgerald DM, Cash CM, Dudley KJ, Sibthorpe PEM, Sillence MN, de Laat MA. (2023). Expression of the GCG gene and secretion of active glucagon-like peptide-1 varies along the length of intestinal tract in horses. Equine Vet J. https://doi.org/10.1111/evj.14020

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Fitzgerald, Danielle M
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Cash, Christina M
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Dudley, Kevin J
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Sibthorpe, Poppy E M
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Sillence, Martin N
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
de Laat, Melody A
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.

Grant Funding

  • DP180102418 / Australian Research Council

References

This article includes 40 references
  1. de Laat MA, McGree JM, Sillence MN. Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation.. Am J Physiol - Endocrinol 2016;310(1):E61-E72.
  2. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP.. Gastroenterology 2007;132(6):2131-2157.
  3. Bamford NJ, Baskerville CL, Harris PA, Bailey SR. Postprandial glucose, insulin, and glucagon-like peptide-1 responses of different equine breeds adapted to meals containing micronized maize.. J Anim Sci 2015;93(7):3377-3383.
  4. Chameroy KA, Frank N, Elliott SB, Boston RC. Comparison of plasma active glucagon-like peptide 1 concentrations in normal horses and those with equine metabolic syndrome and in horses placed on a high-grain diet.. J Equine Vet 2016;40:16-25.
  5. Irwin DM. Variation in the evolution and sequences of proglucagon and the receptors for proglucagon-derived peptides in mammals.. Front Endocrinol 2021;12:12.
  6. Boffelli D, Nobrega MA, Rubin EM. Comparative genomics at the vertebrate extremes.. Nat Rev Genet 2004;5(6):456-465.
  7. Fitzgerald DM, Pollitt CC, Walsh DM, Sillence MN, de Laat MA. The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies.. BMC Vet Res 2019;15(1):345.
  8. Jorsal T, Rhee NA, Pedersen J, Wahlgren CD, Mortensen B, Jepsen SL. Enteroendocrine k and l cells in healthy and type 2 diabetic individuals.. Diabetologia 2018;61(2):284-294.
  9. Eissele R, Göke R, Willemer S, Harthus HP, Vermeer H, Arnold R. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man.. Eur J Clin 1992;22(4):283-291.
  10. Kheder MH, Bailey SR, Dudley KJ, Sillence MN, de Laat MA. Equine glucagon-like peptide-1 receptor physiology.. PeerJ 2018;6:e4316.
  11. Nelson SR, Kim DY, Ericsson AC, Schultz LG, Johnson PJ. GLP-1 secreting l cells in the equine gut.. Havemeyer Equine Laminitis Workshop III 2016; July 9-12; Maui, Hawaii.
  12. Fitzgerald DM, Walsh DM, Sillence MN, Pollitt CC, Laat MA. Insulin and incretin responses to grazing in insulin-dysregulated and healthy ponies.. J Vet Intern Med 2019;33(1):225-232.
  13. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body-fat percentage in mares.. Equine Vet J 1983;15(4):371-372.
  14. Carter RA, Geor RJ, Staniar WB, Cubitt TA, Harris PA. Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies.. Vet J 2009;179(2):204-210.
  15. Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden T. Primer-blast: a tool to design target-specific primers for polymerase chain reaction.. BMC Bioinformatics 2012;13:134.
  16. Sibthorpe PEM. Studies on glucagon-like peptide-2 (GLP-2) and the equine gastrointestinal tract.. Brisbane, Queensland: Queensland University of Technology; 2022.
  17. Panaro BL, Yusta B, Matthews D, Koehler JA, Song Y, Sandoval DA. Intestine-selective reduction of GCG expression reveals the importance of the distal gut for GLP-1 secretion.. Mol Metab 2020;37:100990.
  18. Yang M, Fukui H, Eda H, Xu X, Kitayama Y, Hara K. Involvement of gut microbiota in association between GLP-1/GLP-1 receptor expression and gastrointestinal motility.. Am J Physiol Gastrointest Liver Physiol 2017;312(4):G367-G373.
  19. Holt MK, Richards JE, Cook DR, Brierley DI, Williams DL, Reimann F. Preproglucagon neurons in the nucleus of the solitary tract are the main source of brain GLP-1, mediate stress-induced hypophagia, and limit unusually large intakes of food.. Diabetes 2019;68(1):21-33.
  20. Psichas A, Sleeth ML, Murphy KG, Brooks L, Bewick GA, Hanyaloglu AC. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents.. Int J Obes (Lond) 2015;39(3):424-429.
  21. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2.. Diabetes 2012;61(2):364-371.
  22. Zaborska KE, Dadi PK, Dickerson MT, Nakhe AY, Thorson AS, Schaub CM. Lactate activation of α-cell k(ATP) channels inhibits glucagon secretion by hyperpolarizing the membrane potential and reducing Ca(2+) entry.. Mol Metab 2020;42:101056.
  23. Guedes TP, Martins S, Costa M, Pereira SS, Morais T, Santos A. Detailed characterization of incretin cell distribution along the human small intestine.. Surg Obes Relat Dis 2015;11(6):1323-1331.
  24. Kuhre RE, Deacon CF, Holst JJ, Petersen N. What is an L-cell and how do we study the secretory mechanisms of the L-cell?. Front Endocrinol 2021;12:694284.
  25. Hunt JE, Holst JJ, Jeppesen PB, Kissow H. GLP-1 and intestinal diseases.. Biomedicine 2021;9(4):383.
  26. van Avesaat M, Troost FJ, Ripken D, Hendriks HF, Masclee AAM. Ileal brake activation: macronutrient-specific effects on eating behavior?. Int J Obes (Lond) 2015;39(2):235-243.
  27. Wen J, Phillips SF, Sarr MG, Kost LJ, Holst JJ. PYY and GLP-1 contribute to feedback inhibition from the canine ileum and colon.. Am J Physiol Gastrointest Liver Physiol 1995;269(6):G945-G952.
  28. Destrez A, Grimm P, Julliand V. Dietary-induced modulation of the hindgut microbiota is related to behavioral responses during stressful events in horses.. Physiol Behav 2019;202:94-100.
  29. Adam TC, Westerterp-Plantenga MS. Glucagon-like peptide-1 release and satiety after a nutrient challenge in normal-weight and obese subjects.. Brit J Nutr 2005;93(6):845-851.
  30. Holst JJ. The physiology of glucagon-like peptide 1.. Physiol Rev 2007;87(4):1409-1439.
  31. Cornu M, Modi H, Kawamori D, Kulkarni RN, Joffraud M, Thorens B. Glucagon-like peptide-1 increases beta-cell glucose competence and proliferation by translational induction of insulin-like growth factor-1 receptor expression.. J Biol Chem 2010;285(14):10538-10545.
  32. Koehler JA, Baggio LL, Yusta B, Longuet C, Rowland KJ, Cao X. GLP-1R agonists promote normal and neoplastic intestinal growth through mechanisms requiring FHF7.. Cell Metab 2015;21(3):379-391.
  33. Simonsen L, Pilgaard S, Orskov C, Rosenkilde MM, Hartmann B, Holst JJ. Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats.. Am J Physiol Gastrointest Liver Physiol 2007;293(1):G288-G295.
  34. Frank N, Tadros EM. Insulin dysregulation.. Equine Vet J 2014;46(1):103-112.
  35. Drucker DJ, Boushey RP, Wang F, Hill ME, Brubaker PL, Yusta B. Biologic properties and therapeutic potential of glucagon-like peptide-2.. J Parenter Enteral Nutr 1999;23(5 Suppl):S98-S100.
  36. Schultz NE. Characterization of equine metabolic syndrome and mapping of candidate genetic loci.. [Doctoral]. Minnesota: The University of Minnesota 2016.
  37. Greenwood TA, Kelsoe JR. Promoter and intronic variants affect the transcriptional regulation of the human dopamine transporter gene.. Genomics 2003;82(5):511-520.
  38. Pagani F, Baralle FE. Genomic variants in exons and introns: identifying the splicing spoilers.. Nat Rev Genetics 2004;5(5):389-396.
  39. Torekov SS, Ma L, Grarup N, Hartmann B, Hainerová IA, Kielgast U. Homozygous carriers of the G allele of rs4664447 of the glucagon gene (GCG) are characterised by decreased fasting and stimulated levels of insulin, glucagon and glucagon-like peptide (GLP)-1.. Diabetologia 2011;54(11):2820-2831.
  40. Inbar-Feigenberg M, Choufani S, Butcher DT, Roifman M, Weksberg R. Basic concepts of epigenetics.. Fertil Steril 2013;99(3):607-615.

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.