GLP-2/GLP-2R: Promising Targets for The Short Bowel Syndrome

The sister peptides, glucagon-like peptides 1 and 2 (GLP-1 and -2) are all encoded in the proglucagon gene (GCG). GLP-1 and GLP-2 bind to their respective receptors (GLP-1R & GLP-2R) and play different roles. GLP-1 based therapies are successfully applied for type-2 diabetes (T2D) and obesity, and GLP-2 plays an important role in intestinal growth and adaptation. In recent years, intestinal rehabilitation in patients with short bowel syndrome (SBS) using GLP-2 analogs has made great progress. Compared with the track-crowded GLP-1 field, GLP-2 related research is still a blue ocean waiting for researchers to explore.

Fig. 1 Main products of proglucagon processing
(Wallis K.; et al. Aliment Pharmacol Ther. 2007)

GLP-2 Therapy

Short bowel syndrome (SBS) is a rare malabsorptive disorder mostly secondary to surgical resection of the small intestine. By binding with GLP-2R, GLP-2 can induce the proliferation of intestinal crypt cells, inhibit the apoptosis of intestinal epithelial cells and gastric acid secretion, promote the repair of damaged intestinal mucosa and absorption of intestinal nutrients. Thus, GLP-2 is considered a promising target for the treatment of SBS.

Studies shows that, ileum-resected SBS patients who were given native GLP-2 experienced clinically significant improvements in bowel quality and function. However, due to the short half-life of native GLP-2, the development of long-acting GLP-2 analogs is the main research direction of scientists.

References

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