Glucagon-like peptide-2 (GLP-2) is a naturally occurring hormone produced in the digestive tract that serves a fundamental function in maintaining the health and structure of the intestine. This small, 33-amino-acid peptide is classified as an intestinotrophic agent, meaning it promotes the growth and repair of the intestinal lining. Released in response to the presence of food, GLP-2 acts as a powerful signal to the gut, orchestrating the body’s adaptive response to nutrient intake.
The Peptide’s Role in Intestinal Health
The body produces GLP-2 primarily in enteroendocrine L-cells, which are specialized cells concentrated in the lining of the small intestine and colon. The release of this peptide into the bloodstream is directly triggered by the presence of nutrients in the gut lumen, particularly fats and carbohydrates consumed during a meal.
Promoting Growth and Repair
Once released, GLP-2 exerts its trophic effect by promoting the physical growth and repair of the intestinal mucosa. It achieves this by stimulating the proliferation of cells in the crypts, the base of the intestinal folds where new cells are generated. At the same time, it helps prevent the premature death of existing cells, a process known as apoptosis.
Increasing Absorptive Surface Area
This dual action results in measurable changes in the physical structure of the intestine, specifically an increase in the height of the villi and the depth of the crypts. The villi are the finger-like projections that line the small intestine, and their elongation significantly increases the total surface area available for absorbing nutrients. Furthermore, GLP-2 strengthens the integrity of the intestinal barrier, reducing its permeability and helping to prevent harmful substances from passing into the bloodstream.
Therapeutic Applications in Digestive Disorders
The native form of GLP-2 is quickly broken down in the body by the enzyme dipeptidyl peptidase IV (DPP-IV), giving it a very short lifespan. To harness its growth-promoting properties for medical use, scientists developed a synthetic analog called teduglutide, which is resistant to this rapid degradation. This modification allows for a prolonged half-life, making once-daily dosing possible for patients.
Short Bowel Syndrome (SBS)
The primary application for this therapeutic approach is in managing Short Bowel Syndrome (SBS), a severe condition characterized by malabsorption that occurs after a large portion of the small intestine has been surgically removed or lost due to disease. Patients with SBS often cannot absorb enough nutrients and fluids from food to sustain life, leading to dependence on intravenous feeding, known as Parenteral Nutrition (PN). The GLP-2 analog enhances the remaining bowel’s ability to adapt and function more effectively. This adaptive effect helps the remaining intestine absorb more water, electrolytes, and energy from the patient’s diet.
Other Conditions
Beyond SBS, this mechanism of enhancing mucosal integrity has also been investigated for potential use in other conditions where the gut lining is compromised. These include complications of severe Crohn’s disease or other forms of inflammatory bowel disease where the promotion of healing in the gastrointestinal tract is desirable.
Administering GLP-2 Therapy and Expected Outcomes
The synthetic GLP-2 analog is administered as a subcutaneous injection, typically given once a day. Treatment is generally initiated only after a patient has stabilized following the initial surgical recovery and natural adaptive period, often six months or more after the bowel resection.
Reducing PN Dependence
The main clinical objective of this therapy is to reduce or eliminate a patient’s reliance on Parenteral Nutrition. Clinical success is measured by a significant reduction in the volume of PN required, and in some cases, complete weaning off intravenous support. This increased absorption can also diminish the excessive fluid loss experienced as diarrhea, a characteristic challenge of SBS.
Monitoring and Side Effects
Common side effects observed with the therapy include abdominal pain and reactions at the injection site, which are generally mild. Clinicians must also monitor patients closely for fluid overload, as the drug’s effect of increasing fluid absorption necessitates prompt adjustment of PN and fluid input. Patients with an intact colon must undergo regular colonoscopy screenings due to a theoretical concern of accelerated cell growth.