دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Expression of the GCG gene and secretion of active glucagon-like peptide-1 varies along the length of intestinal tract in horses.
المؤلفون: Fitzgerald DM; Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia., Cash CM; Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia., Dudley KJ; Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia., Sibthorpe PEM; Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia., Sillence MN; Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia., de Laat MA; Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
المصدر: Equine veterinary journal [Equine Vet J] 2024 Mar; Vol. 56 (2), pp. 352-360. Date of Electronic Publication: 2023 Oct 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: United States NLM ID: 0173320 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2042-3306 (Electronic) Linking ISSN: 04251644 NLM ISO Abbreviation: Equine Vet J Subsets: MEDLINE
أسماء مطبوعة: Publication: <2009- > : Hobokken, NJ : Wiley
Original Publication: Newmarket, Suffolk : Equine Veterinary Journal, Ltd
مواضيع طبية MeSH: Glucagon-Like Peptide 1*/genetics , Insulin*/metabolism, Humans ; Animals ; Horses/genetics ; Intestine, Small/metabolism ; Proglucagon/genetics ; Proglucagon/analysis ; Proglucagon/metabolism ; Polymerase Chain Reaction/veterinary
مستخلص: Background: 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.
Objectives: 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.
Study Design: 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.
Main Limitations: 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.)
References: 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.
Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131-2157.
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.
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.
Irwin DM. Variation in the evolution and sequences of proglucagon and the receptors for proglucagon-derived peptides in mammals. Front Endocrinol. 2021;12:12.
Boffelli D, Nobrega MA, Rubin EM. Comparative genomics at the vertebrate extremes. Nat Rev Genet. 2004;5(6):456-465.
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.
Jorsal T, Rhee NA, Pedersen J, Wahlgren CD, Mortensen B, Jepsen SL, et al. Enteroendocrine k and l cells in healthy and type 2 diabetic individuals. Diabetologia. 2018;61(2):284-294.
Eissele R, Göke R, Willemer S, Harthus HP, Vermeer H, Arnold R, et al. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin. 1992;22(4):283-291.
Kheder MH, Bailey SR, Dudley KJ, Sillence MN, de Laat MA. Equine glucagon-like peptide-1 receptor physiology. PeerJ. 2018;6:e4316.
Nelson SR, Kim DY, Ericsson AC, Schultz LG, Johnson PJ. GLP-1 secreting l cells in the equine gut. Havemeyer Equine Laminitis Workshop III; July 9-12; Maui, Hawaii. 2016.
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.
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.
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.
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.
Sibthorpe PEM. Studies on glucagon-like peptide-2 (GLP-2) and the equine gastrointestinal tract. Brisbane, Queensland: Queensland University of Technology; 2022.
Panaro BL, Yusta B, Matthews D, Koehler JA, Song Y, Sandoval DA, et al. Intestine-selective reduction of GCG expression reveals the importance of the distal gut for GLP-1 secretion. Mol Metab. 2020;37:100990.
Yang M, Fukui H, Eda H, Xu X, Kitayama Y, Hara K, et al. 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.
Holt MK, Richards JE, Cook DR, Brierley DI, Williams DL, Reimann F, et al. 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.
Psichas A, Sleeth ML, Murphy KG, Brooks L, Bewick GA, Hanyaloglu AC, et al. 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.
Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61(2):364-371.
Zaborska KE, Dadi PK, Dickerson MT, Nakhe AY, Thorson AS, Schaub CM, et al. 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.
Guedes TP, Martins S, Costa M, Pereira SS, Morais T, Santos A, et al. Detailed characterization of incretin cell distribution along the human small intestine. Surg Obes Relat Dis. 2015;11(6):1323-1331.
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.
Hunt JE, Holst JJ, Jeppesen PB, Kissow H. GLP-1 and intestinal diseases. Biomedicine. 2021;9(4):383.
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.
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.
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.
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.
Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409-1439.
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.
Koehler JA, Baggio LL, Yusta B, Longuet C, Rowland KJ, Cao X, et al. GLP-1R agonists promote normal and neoplastic intestinal growth through mechanisms requiring FHF7. Cell Metab. 2015;21(3):379-391.
Simonsen L, Pilgaard S, Orskov C, Rosenkilde MM, Hartmann B, Holst JJ, et al. 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.
Frank N, Tadros EM. Insulin dysregulation. Equine Vet J. 2014;46(1):103-112.
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.
Schultz NE. Characterization of equine metabolic syndrome and mapping of candidate genetic loci. [Doctoral]. Minnesota: The University of Minnesota 2016.
Greenwood TA, Kelsoe JR. Promoter and intronic variants affect the transcriptional regulation of the human dopamine transporter gene. Genomics. 2003;82(5):511-520.
Pagani F, Baralle FE. Genomic variants in exons and introns: identifying the splicing spoilers. Nat Rev Genetics. 2004;5(5):389-396.
Torekov SS, Ma L, Grarup N, Hartmann B, Hainerová IA, Kielgast U, et al. 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.
Inbar-Feigenberg M, Choufani S, Butcher DT, Roifman M, Weksberg R. Basic concepts of epigenetics. Fertil Steril. 2013;99(3):607-615.
معلومات مُعتمدة: DP180102418 Australian Research Council
فهرسة مساهمة: Keywords: GLP-1; enteroinsular; horse; hyperinsulinaemia; incretin; laminitis; proglucagon
المشرفين على المادة: 89750-14-1 (Glucagon-Like Peptide 1)
0 (Insulin)
55963-74-1 (Proglucagon)
تواريخ الأحداث: Date Created: 20231019 Date Completed: 20240214 Latest Revision: 20240214
رمز التحديث: 20240214
DOI: 10.1111/evj.14020
PMID: 37853957
قاعدة البيانات: MEDLINE
الوصف
تدمد:2042-3306
DOI:10.1111/evj.14020