Gastrointestinal defense mechanisms

Abstract

Purpose of Review To summarize and illuminate the recent findings regarding gastroduodenal mucosal defense mechanisms and the specific biomolecules involved in regulating this process, such as glucagon-like peptides (GLPs). Recent Findings There has been a growing interest in luminal nutrient chemosensing and its physiological effects throughout the digestive system. From the ingestion of food in the oral cavity to the processing and absorption of nutrients in the intestines, nutrient chemosensing receptors signal the production and release of numerous bioactive peptides from enteroendocrine cells, such as the proglucagon-derived peptides. There has been a major emphasis on two proglucagon-derived peptides, namely GLPs 1 & 2, due to their apparent beneficial effect on gut structure, function, and on metabolic processes. As an incretin, GLP-1 not only enhances the effect and release of insulin on pancreaticβcells, but also has been implicated in having trophic effects on the intestinal epithelium. Additionally, GLP-2, the other major proglucagon-derived peptide, has potent intestinotrophic effects, such as increasing the rate of mucosal stem cell proliferation, mucosal blood flow, and fluid absorption, as well as augmenting the rate of duodenal bicarbonate secretion in order to improve gastric mucosal health and longevity. Summary Understanding the mechanisms underlying nutrient chemosensing and how it relates to GLP release can further elucidate how the gut functions in response to cellular changes and disturbances. Furthermore, a more in-depth comprehension of GLP release and its tissue-specific effects will help improve the utility of GLP-1 & -2 receptor agonists in clinical settings. This, in turn, should help patients suffering from intestinal failure, malabsorption, and mucosal injury.

The Gastroprotective Effect of Small Molecule Oligopeptides Isolated from Walnut (Juglans regia L.) against Ethanol-Induced Gastric Mucosal Injury in Rats

“…Gastric mucosal injury is a multifactorial pathological process that involved endogenous and exogenous factors, its basic pathophysiology mechanism includes imbalance between some pro-inflammation factors (including hydrochloric acid, pepsin, and reactive oxygen species) and defensive factors (such as mucus-bicarbonate barrier, mucosal blood flow, and some cytokines) [35][36][37][38]. Although the complex pathological mechanism of ethanol-induced gastric mucosal damage, the interaction of gastric acid and pepsin is still considered to be the major cause of gastric mucosal injury [39].…”

Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity

“…Among cohorts in the current study, 23–52% of individuals were taking DPP4-inhibitors or GLP-1 receptor agonists. We cannot exclude that these antidiabetic therapies could influence EEC differentiation through intestinal hypertrophy as reviewed in [ 50 ]. However, here we observed an impaired EEC differentiation and GLP-1 cell density whose are in opposite with an intestinotrophic effect.…”

Fermented vegetable and fruit extract (OM-X®) stimulates murine gastrointestinal tract cells and RAW264.7 cells in vitro and regulates liver gene expression in vivo

“…Toll-like receptors (TLRs) 2, 4, and 6 are involved in macrophage activation by pathogen-associated molecular patterns (PAMPs). For example, certain microbe-derived substances, including β-glucan and lipopolysaccharides, stimulate these receptors and thereby promote production of cytokines, like IL-1, IL-6, IL-12, and TNF-α [10,11].…”