The pivotal relation between glucagon-like peptides, NFκB and inflammatory bowel disease.

Glucagon-like peptides (GLPs), GLP-1 and GLP-2, are released from intestinal enteroendocrine cells (L cells) in response to ingested nutrients. GLP-1 plays a crucial role in lowering blood glucose and controlling body weight, through stimulating the islet ß cells of pancreas to secrete insulin, inhibiting gastric emptying, and reducing food ingestion. Therefore, GLP-1 receptor agonists are now used in the treatment of obese patients with type 2 diabetes mellitus (T2DM). GLP-2, on the other hand, is used as a novel therapy for short bowel syndrome (SBS) through its ability to restore intestinal homeostasis and induce epithelial proliferation. GLPs and the inhibitors of their degradation enzymes, dipeptidyl peptidase-IV (DPP-IV) inhibitors, have many anti-inflammatory actions. Many animal-based clinical trials have proved that GLP-based therapy has a pivotal role in the management of inflammatory bowel disease (IBD), possibly through regulating the transcription factor nuclear factor kappa-ligand B (NFκB). NFκB controls the production and secretion of many cytokines and chemokines encountered in the pathophysiology of IBD such as interleukin (IL-1β-IL-12, IL-13, IL-21, IL-22, IL-6) and tumour necrosis factor-alpha (TNF-α) and hence, may provide a promising therapeutic option.