Glucagon-like peptide-2 (GLP-2) is an intestinal-specific nutritional factor that exerts its effects through its receptor. Cells that can respond to GLP-2 include enterocytes, goblet cells, neurons, subepithelial fibroblasts, endothelial cells, and certain enteroendocrine cells. GLP-2 is generated by the cleavage of proglucagon in the intestine and brain. Some researchers believe that GLP-2 may be widely degraded in the human body by dipeptidyl peptidase IV (DPP-IV) to produce the inactive form GLP-2(3-33). In recent years, studies have found that GLP-2 not only affects various systems to different extents but also has specific effects on the gastrointestinal tract. GLP-2 was discovered by Lilly Laboratories in the United States while cloning the proglucagon gene. It is a member of the pituitary adenylate cyclase-activating peptide/glucagon superfamily and is a single-chain peptide consisting of 33 amino acids (AA), with a molecular weight of approximately 3900 Da. The second position at the N-terminus is an alanine residue, which makes it prone to degradation by the peptidase enzyme dipeptidyl peptidase-IV.

Its half-life is approximately 7 minutes. The amino acid sequence of GLP-2 is highly homologous and conserved across mammals. Amino acid sequence of GLP-2. Promote Intestinal Repair and Growth: GLP-2 stimulates the proliferation and differentiation of intestinal epithelial cells, promoting intestinal repair and growth, especially during recovery after intestinal injury or disease. This function makes it potentially valuable in the treatment of conditions like short bowel syndrome and post-surgical recovery. Improve Intestinal Barrier Function: GLP-2 enhances the tight junctions between intestinal epithelial cells, thereby strengthening the intestinal barrier. This helps prevent harmful substances (such as pathogens and toxins) from entering the bloodstream and reduces intestinal permeability (leaky gut). Promote Intestinal Absorptive Function: GLP-2 increases the length and surface area of intestinal villi, thereby improving the absorptive capacity of the intestine, particularly for water, electrolytes, nutrients, and minerals. This enhances digestive and absorptive functions. Increase Mesenteric Blood Flow: GLP-2 increases the blood flow to the mesentery, improving the blood supply to the intestine.

This enhances the delivery of oxygen and nutrients to the intestinal tissue, further promoting intestinal function and recovery. Inhibit Gastrointestinal Motility: GLP-2 has the effect of inhibiting gastrointestinal motility, which is beneficial in reducing diarrhea, alleviating intestinal inflammation, and easing gastrointestinal discomfort. In certain gastrointestinal diseases, GLP-2 may help improve intestinal motility. Regulate Intestinal Endocrine Function: GLP-2 can regulate the secretion of intestinal hormones, influencing the digestive and absorptive functions of the gastrointestinal tract. For example, it can affect gastric acid secretion and pancreatic fluid secretion, helping maintain the balance of the gastrointestinal environment. GLP-1:Primarily regulates blood glucose levels by promoting insulin secretion and inhibiting glucose production. It has effects on slowing gastric emptying and suppressing appetite, which helps in controlling body weight. GLP-1 plays a key role in regulating blood sugar levels, insulin sensitivity, and improving insulin resistance. GLP-2:Primarily acts on the intestine, MedicGLP promoting the growth and repair of intestinal cells, and increasing the surface area of the intestine to improve nutrient absorption.GLP-2 enhances intestinal barrier function, reduces gut permeability, HOME and aids in intestinal recovery, particularly following intestinal injury or surgery.

GLP-1:Mainly secreted by L cells in the intestines, with secretion increasing especially after food intake, particularly when carbohydrates and fats are consumed. GLP-2:Primarily secreted by intestinal neurons and endocrine cells, and its secretion is also stimulated by nutrients in the gastrointestinal tract. GLP-2:Primarily acts on intestinal epithelial cells, promoting their growth and repair, thus enhancing intestinal absorption functions.GLP-2 also increases the intestinal surface area, improving the absorption of nutrients, including water, electrolytes, and minerals. Grelaplutide: Grelaplutide is another long-acting GLP-2 analog that is currently in the research stage, primarily being investigated for the treatment of inflammatory bowel disease (IBD) and Crohn's disease. It works by reducing intestinal inflammation while promoting intestinal absorption and repair, helping to improve the nutritional status of patients. Studies on Grelaplutide suggest that it not only plays a role in reducing intestinal inflammation but also enhances the intestinal barrier function, potentially improving treatment outcomes for patients with chronic intestinal diseases. Teduglutide: Teduglutide (brand name Gattex) is currently the most well-known GLP-2 agonist, Medic GLP Official approved for the treatment of Short Bowel Syndrome (SBS), a condition that leads to severe malabsorption of nutrients.

As a recombinant version of GLP-2, Teduglutide has a long-lasting effect. It works by activating GLP-2 receptors, promoting the proliferation of intestinal epithelial cells, enhancing the integrity of the intestinal barrier, and helping restore intestinal absorption function. Teduglutide (Brand name: Revestive): Teduglutide is the most well-known GLP-2 analogue and has been approved for the treatment of parenteral nutrition (PN)-dependent short bowel syndrome. It promotes intestinal repair and enhances intestinal absorption function. Teduglutide prevents the degradation of GLP-2, thus prolonging its action time and helping to improve intestinal function and reduce dependence on parenteral nutrition. Apreglutide (Brand name: APRA): MedicGLP daily capsules Apreglutide is another GLP-2 analogue with a longer half-life, currently undergoing clinical studies. It is primarily used for the treatment of gastrointestinal diseases and intestinal dysfunction. Glepaglutide: Glepaglutide is a novel GLP-2 analogue with similar functions. It is under clinical trials to explore its applications in gastrointestinal-related diseases. ZP1849: ZP1849 is another GLP-2 analogue in development, designed to enhance intestinal absorption function and treat diseases related to intestinal damage.