Glucagon-like peptide-2 (GLP-2) is a hormone produced primarily by specialized L-cells in the small and large intestines, and also in the brain. Its release is triggered by the presence of nutrients in the gut after a meal. This 33-amino acid peptide plays a role in digestive system health.
Understanding GLP-2’s Role in Gut Health
GLP-2 promotes the growth and repair of the intestinal lining, known as the mucosa. It does this by increasing the multiplication of intestinal epithelial cells and reducing apoptosis in these cells. This action helps maintain a healthy gut barrier.
The hormone also improves nutrient absorption by increasing the surface area of the intestinal lining, which is lined with tiny finger-like projections called villi. GLP-2 enhances villous height and crypt depth, leading to a more efficient uptake of nutrients. This is beneficial in conditions where nutrient absorption is compromised.
GLP-2 strengthens the gut barrier, reducing its permeability. A strong barrier prevents harmful bacteria and toxins from leaking from the gut into the bloodstream, thereby supporting overall immune health. This is accomplished by promoting the expression of tight junction proteins, which seal the spaces between intestinal cells.
GLP-2 can also slow down gastrointestinal motility, allowing more time for nutrient absorption and helping reduce symptoms like diarrhea. It also helps reduce inflammation within the digestive tract by inhibiting pro-inflammatory cytokines and promoting anti-inflammatory cytokines.
Medical Uses of GLP-2 Analogues
Synthetic versions of GLP-2, known as analogues, are used clinically to manage conditions affecting gut function. These analogues are designed to be more resistant to degradation in the body, allowing for a longer-lasting effect compared to naturally occurring GLP-2, which has a half-life of approximately 7 minutes.
A primary application is in Short Bowel Syndrome (SBS), a condition where a substantial portion of the small intestine has been surgically removed, leading to severe malabsorption. An analogue called teduglutide has been approved for SBS treatment. Teduglutide works by enhancing intestinal adaptation, promoting the growth of the remaining bowel, and improving its ability to absorb fluids and nutrients. This can reduce or eliminate the need for parenteral nutrition, which is intravenous feeding.
GLP-2 analogues are also being explored for their potential in inflammatory bowel diseases (IBD) like Crohn’s disease. These diseases involve chronic inflammation of the gastrointestinal tract. GLP-2’s ability to promote mucosal healing and its anti-inflammatory properties suggest it could be a beneficial treatment option for these conditions, potentially leading to a reduction in inflammation and improved gut integrity.
Important Considerations and Next Steps
GLP-2 analogues are administered through subcutaneous injections, often once a day. Common side effects include abdominal pain, abdominal distension, nausea, and reactions at the injection site. Less frequent side effects include headache, flatulence, or decreased appetite.
Ongoing research continues to explore the full potential of GLP-2. Newer, longer-acting analogues, such as apraglutide and glepaglutide, are in various stages of clinical development, with some having half-lives of 70-80 hours, allowing for less frequent administration (e.g., once every three to seven days). Future investigations may also focus on the combined use of GLP-2 with other peptides, such as GLP-1, for enhanced treatment outcomes in intestinal conditions.