Glucagon-Like Peptide 2 (GLP-2), a biologically active peptide secreted by the L-type enteroendocrine cells of the intestinal epithelium, has already shown therapeutic efficacy in several animal models of chronic intestinal disease. In addition, GLP-2 has been reported to enhance morphological and functional indexes of recovery following acute intestinal injury indexed by exposure to either 5-fluorouracil or nonsteroidal anti-inflammatory drugs.
An Overview of Glucagon-Like Peptide 2 (GLP-2)
Glucagon-like peptide 2 (GLP-2) is an intestinal peptide hormone with a variety of intestinal effects, such as stimulating intestinal mucosal growth, promoting digestion and absorption of nutrients, improving intestinal barrier function, and inhibiting gastric motility. GLP-2 is a gut-specific trophic factor that promotes crypt cell proliferation and inhibits apoptosis to promote intestinal growth. GLP-2 is a single-chain polypeptide consisting of 33 amino acid residues. Its amino acid sequence is in the 126th to 158th positions, and its relative molecular mass is about 3,900. Its amino acid sequence is highly conserved in mammals. The regulation of glutular nutrition by GLP-2 involves a variety of cell signal transduction pathways, including cAMP/PKA pathway, PI3K/Akt pathway and Wnt/β-catenin pathway, among which cAMP/PKA pathway is the main pathway. These pathways coordinate with each other to regulate the homeostasis and intestinal adaptation of intestinal epithelial cells.
Major type of GLP-2
There are two main molecular forms of GLP-2: active GLP-2-(1-33) and inactive GLP-2-(3-33).
GLP-2 and diseases
Currently, GLP-2 is used in clinical trial treatment of various intestinal diseases. GLP-2 can stimulate the growth of intestinal mucosa and regeneration after injury. GLP-2 also inhibits gastric acid secretion and gastric movement, stimulates intestinal nutrient transport and intestinal digestive enzyme activity. Thereby improving the barrier function of the intestinal tract, stimulating blood circulation of the intestinal mucosa, and improving the utilization rate of nutrition. The trophic effect of GLP-2 on small intestinal and large intestinal epithelial cells is achieved by stimulating crypt cell proliferation and delaying cell apoptosis, regulating intestinal glucose transport receptor activity, reducing gastric emptying and gastric acid secretion. Studies have shown that GLP-2 reduces enteritis and damage by activating neurons that produce vasoactive intestinal peptide (VIP). GLP-2 reduces levels of inflammatory cytokines (such as interferon γ, tumor necrosis factor α, interleukin 1β) and increases the production of the anti-inflammatory cytokine interleukin-10. This is associated with an increase in the number of neurons expressing VIP in the submucosal plexus. Therefore, GLP-2 has broad prospects as an enteral nutrition factor.
Dubé P.E., Brubaker P.L. (2007) Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators. Am J Physiol Endocrinol Metab, 293(2): 460-465.