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

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