GLP-2: What do we know? What are we going to discover?

Baldassano, Sara; Amato, Antonella

doi:10.1016/j.regpep.2014.09.002

Cited by 41 publications

(15 citation statements)

References 71 publications

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“…GLP-2 is a major driver of intestinal adaptation [ 41 , 42 ] and a long-acting analogue, teduglutide, has been shown in clinical trials to augment intestinal adaptation in patients with short bowel [ 43 ]. GLP-2 is secreted by L cells of the distal gut, probably in response to nutrients that have not been absorbed proximally.…”

Section: Discussionmentioning

confidence: 99%

Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy

et al. 2016

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IntroductionEnvironmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms.MethodsWe studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test.ResultsCLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins.ConclusionsConfocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE.

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Section: Discussionmentioning

confidence: 99%

Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy

et al. 2016

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“…Indeed, GLP2 (3-33) may act as a weak agonist at pharmacological concentrations (Shin et al 2005); however, it is able to act as a competitive antagonist of the GLP2 receptor (GLP2R) in rodents (Thulesen et al 2002, Shin et al 2005. Then DPP-IV-resistant GLP2 analogues, such as [Gly 2 ]-GLP2 (teduglutide), exhibit greater bioactivity relative to native molecule, due to their longer circulating half-lives (Tavares et al 2000, Baldassano & Amato 2014. GLP2 promotes energy absorption within the gastrointestinal tract through non-specific and specific adaptation.…”

Section: Overview On Glp2mentioning

confidence: 99%

GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity

Amato¹,

Baldassano²,

Mulè³

2016

Journal of Endocrinology

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Glucagon-like peptide 2 (GLP2) is a proglucagon-derived peptide produced by intestinal enteroendocrine L-cells and by a discrete population of neurons in the brainstem, which projects mainly to the hypothalamus. The main biological actions of GLP2 are related to the regulation of energy absorption and maintenance of mucosal morphology, function and integrity of the intestine; however, recent experimental data suggest that GLP2 exerts beneficial effects on glucose metabolism, especially in conditions related to increased uptake of energy, such as obesity, at least in the animal model. Indeed, mice lacking GLP2 receptor selectively in hypothalamic neurons that express proopiomelanocortin show impaired postprandial glucose tolerance and hepatic insulin resistance (by increased gluconeogenesis). Moreover, GLP2 acts as a beneficial factor for glucose metabolism in mice with high-fat diet-induced obesity. Thus, the aim of this review is to update and summarize current knowledge about the role of GLP2 in the control of glucose homeostasis and to discuss how this molecule could exert protective effects against the onset of related obesity type 2 diabetes.

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“…These peptide hormones have a variety of functions, including effects on epithelial cell proliferation, inflammation, and consequently intestinal barrier integrity. One of these hormones is glucagon-like peptide-2 (GLP-2), a hormone that is important in maintaining epithelial integrity ( 11 ). The enteroendocrine cells are activated by various luminal signals, including bacterial signals (see below).…”

Section: Role Of the Intestinal Barrier In Gut Healthmentioning

confidence: 99%

Steering Endogenous Butyrate Production in the Intestinal Tract of Broilers as a Tool to Improve Gut Health

et al. 2015

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The ban on antimicrobial growth promoters and efforts to reduce therapeutic antibiotic usage has led to major problems of gastrointestinal dysbiosis in livestock production in Europe. Control of dysbiosis without the use of antibiotics requires a thorough understanding of the interaction between the microbiota and the host mucosa. The gut microbiota of the healthy chicken is highly diverse, producing various metabolic end products, including gases and fermentation acids. The distal gut knows an abundance of bacteria from within the Firmicutes Clostridium clusters IV and XIVa that produce butyric acid, which is one of the metabolites that are sensed by the host as a signal. The host responds by strengthening the epithelial barrier, reducing inflammation, and increasing the production of mucins and antimicrobial peptides. Stimulating the colonization and growth of butyrate-producing bacteria thus may help optimizing gut health. Various strategies are available to stimulate butyrate production in the distal gut. These include delivery of prebiotic substrates that are broken down by bacteria into smaller molecules which are then used by butyrate producers, a concept called cross-feeding. Xylo-oligosaccharides (XOS) are such compounds as they can be converted to lactate, which is further metabolized to butyrate. Probiotic lactic acid producers can be supplied to support the cross-feeding reactions. Direct feeding of butyrate-producing Clostridium cluster IV and XIVa strains are a future tool provided that large scale production of strictly anaerobic bacteria can be optimized. Current results of strategies that promote butyrate production in the gut are promising. Nevertheless, our current understanding of the intestinal ecosystem is still insufficient, and further research efforts are needed to fully exploit the capacity of these strategies.

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GLP-2: What do we know? What are we going to discover?

Cited by 41 publications

References 71 publications

Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy

Endomicroscopic and Transcriptomic Analysis of Impaired Barrier Function and Malabsorption in Environmental Enteropathy

GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity

Steering Endogenous Butyrate Production in the Intestinal Tract of Broilers as a Tool to Improve Gut Health

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