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

• Published in: Equine veterinary journal Vol. 56; no. 2; pp. 352 - 360
• Main Authors: Fitzgerald, Danielle M., Cash, Christina M., Dudley, Kevin J., Sibthorpe, Poppy E. M., Sillence, Martin N., Laat, Melody A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-03-2024
• Subjects: enteroinsular; GLP‐1; Glucagon; horse; Horses; hyperinsulinaemia; incretin; laminitis; Peptides; proglucagon; horse; GLP-1; enteroinsular; proglucagon; incretin; laminitis; hyperinsulinaemia
• ISSN: 0425-1644; 2042-3306
• DOI: 10.1111/evj.14020

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.