Glucagon-like peptide-2 (GLP-2) is a naturally occurring hormone primarily produced in the gut by L-cells located in the small intestine and colon. Its secretion is triggered by the presence of nutrients from ingested food. GLP-2 plays a significant role in maintaining the health and function of the digestive system.
The Natural Role of GLP-2
GLP-2 is an intestinotrophic hormone that promotes the growth of intestinal tissue. It stimulates the proliferation of epithelial cells and reduces programmed cell death, supporting a healthy gut lining and increasing its surface area for improved nutrient absorption.
The hormone also enhances the integrity of the gut barrier, a structure that prevents harmful bacteria and toxins from entering the bloodstream. It achieves this by promoting the expression of tight junction proteins, which seal the spaces between intestinal cells. GLP-2 additionally influences gastrointestinal motility, slowing the movement of food through the digestive tract to further aid nutrient absorption.
GLP-2 and GLP-1: A Key Distinction
While both GLP-2 and Glucagon-like peptide-1 (GLP-1) are gut peptides co-secreted in response to food, they have distinct primary functions. GLP-1 is recognized for regulating blood sugar and promoting weight loss. It stimulates glucose-dependent insulin secretion from the pancreas and suppresses glucagon release, a hormone that raises blood sugar. GLP-1 also slows gastric emptying, which helps reduce post-meal blood sugar spikes.
GLP-1 also acts on the brain to regulate appetite, increasing feelings of fullness and reducing food intake. Medications that mimic GLP-1, known as GLP-1 receptor agonists like semaglutide and liraglutide, are approved for managing type 2 diabetes and obesity due to these effects. In contrast, GLP-2’s main actions focus on the structural integrity and absorptive capacity of the gastrointestinal tract, rather than direct blood sugar control or significant appetite suppression for weight loss.
How GLP-2 Influences Metabolism and Weight
GLP-2 is not considered a primary medication for significant weight reduction in the same way that GLP-1 agonists are. However, its actions in the gut can indirectly affect metabolic health. By promoting the growth and repair of the intestinal lining, GLP-2 enhances the efficiency of nutrient absorption.
This improved absorption can contribute to better overall nutritional status. GLP-2 also strengthens the gut barrier, reducing intestinal permeability and limiting the passage of inflammatory substances from the gut into the bloodstream. Reducing gut inflammation may have positive secondary implications for metabolic function, as chronic low-grade inflammation is linked to metabolic disorders. GLP-2 has also been shown to slow gastrointestinal motility and may influence appetite by affecting gut-brain communication, though consistent appetite-suppressing effects in humans are still under investigation.
Current Medical Uses of GLP-2 Analogues
Synthetic versions of GLP-2, known as GLP-2 analogues, have approved medical applications, particularly for conditions characterized by impaired intestinal function. Teduglutide, marketed as Revestive or Gattex, is a prominent example. It is a prescription medication used to treat short bowel syndrome (SBS) in adults and children aged one year or older who rely on parenteral support.
SBS is a severe condition resulting from the surgical removal of a significant portion of the small intestine, leading to malabsorption of nutrients and fluids. Teduglutide works by improving intestinal absorptive capacity, promoting mucosal growth, and potentially restoring gastric emptying and secretion. This helps reduce the need for intravenous feeding and improves the patient’s ability to absorb nutrients from food, enhancing intestinal rehabilitation.