Expression of the GCG gene and secretion of active glucagon-like peptide-1 varies along the length of intestinal tract in horses.
Authors: Fitzgerald Danielle M, Cash Christina M, Dudley Kevin J, Sibthorpe Poppy E M, Sillence Martin N, de Laat Melody A
Journal: Equine veterinary journal
Summary
# Editorial Summary Active glucagon-like peptide-1 (aGLP-1) has emerged as a potential factor in equine insulin dysregulation, yet the mechanisms underlying its elevation remain poorly understood. Fitzgerald and colleagues examined whether genetic variation in the GCG gene—which encodes the proglucagon precursor cleaved to produce aGLP-1—might explain the elevated post-prandial aGLP-1 concentrations observed in dysregulated horses, whilst simultaneously mapping GCG expression and aGLP-1 secretion across different intestinal segments using droplet digital PCR and tissue explant studies. Horses with insulin dysregulation demonstrated significantly higher median post-prandial aGLP-1 (10.2 pmol/L versus 8.47 pmol/L; p=0.03), yet genomic sequencing revealed complete sequence identity of GCG exons between dysregulated and healthy animals, indicating that the elevated hormone concentrations were not attributable to genetic mutations. Critical to understanding GLP-1 physiology, GCG expression and aGLP-1 secretion varied substantially across the intestinal tract (p<0.001), with both small and large intestine contributing to active hormone production. These findings suggest that dysregulation of aGLP-1 in susceptible horses stems from altered gene expression or secretory function rather than structural genetic defects, redirecting clinical investigation towards dietary, microbial and physiological factors that modulate intestinal L-cell activity.
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Practical Takeaways
- •Insulin dysregulation in horses is associated with elevated glucagon-like peptide-1 secretion, but this is not caused by genetic mutations in the GCG gene—consider other metabolic or regulatory factors in ID management
- •Both small and large intestine contribute to GLP-1 production in horses; understanding the full intestinal contribution may help explain variable responses to dietary interventions in ID horses
- •Current findings suggest that ID management strategies should focus on metabolic regulation and intestinal function rather than genetic factors affecting GCG expression
Key Findings
- •Post-prandial aGLP-1 concentrations were significantly higher in horses with insulin dysregulation (10.2 pmol/L) compared to healthy horses (8.47 pmol/L, p=0.03)
- •100% pairwise identity of GCG gene exons between horses with and without insulin dysregulation, indicating differences in aGLP-1 are not due to genetic variation
- •GCG mRNA expression and aGLP-1 secretion varied significantly along the intestinal tract (p<0.001), with both small and large intestine being secretion sites
- •Elevated aGLP-1 in insulin dysregulation is likely due to post-transcriptional mechanisms rather than GCG gene mutations