Disease relevance of Mcpt10

• Preliminary human studies indicate that GLP-2 may enhance energy absorption and reduce fluid loss in subjects with short bowel syndrome suggesting that GLP-2 functions as a key regulator of mucosal integrity, permeability, and nutrient absorption [1].
• TPN plus GLP-2 treatment resulted in increased bowel and body weight, villus height, intestinal mucosal surface area, CCP, and reduced intestinal permeability compared with the TPN alone animals (P < 0.05) [2].
• The enhanced uptake of fatty acids with GLP-2 plus Dex was not explained by alterations in the animals' body or intestinal weights, intestinal morphology, or intestinal- or liver-fatty acid binding proteins [3].
• CONCLUSION: GLP-2 treatment significantly decreases intestinal permeability in acute pancreatitis [4].
• METHODS: To examine whether GLP-2 can decrease intestinal permeability and thereby decrease BT in acute necrotizing pancreatitis, 34 male Sprague-Dawley rats (200 to 300 g) were studied [4].

High impact information on Mcpt10

• GLP-2 stimulated crypt cell proliferation and consistently induced a marked increase in bowel weight and villus growth of the jejunum and ileum that was evident within 4 days after initiation of GLP-2 administration [5].
• GLP-1 is implicated in the control of insulin secretion, food intake, and satiety signaling, and GLP-2 is implicated in regulating small-bowel growth [6].
• Although GLP-2 stimulated both cAMP accumulation and cell proliferation, 8-bromo-cyclic AMP alone did not promote cell proliferation [7].
• Glucagon-like peptide-2 (GLP-2) promotes the expansion of the intestinal epithelium through stimulation of the GLP-2 receptor, a recently identified member of the glucagon-secretin G protein-coupled receptor superfamily [7].
• Although activation of G protein-coupled receptors may lead to stimulation of cell growth, the mechanisms transducing the GLP-2 signal to mitogenic proliferation remain unknown [7].

Chemical compound and disease context of Mcpt10

• Recent studies suggest that treatment with glucagon-like peptide-2 (GLP-2), which is synthesized in the intestine and released after food intake, elicits mucosal hyperplasia in the small intestine of rodents and prevents parenteral nutrition-induced gut hypoplasia [8].

Biological context of Mcpt10

• GLP-1 promotes efficient nutrient assimilation while GLP-2 regulates energy absorption via effects on nutrient intake, gastric acid secretion and gastric emptying, nutrient absorption, and mucosal permeability [1].
• Thus GLP-2 can maintain small intestinal morphology and function, but effects on gene expression are not mediated by gross changes in the level of the mRNA for the homeobox protein Cdx-2 [9].
• The amino acid sequence deduced from the cDNA consists of 248 residues and shows 88.2% identity to GLP I and 50.6% identity to GLP II [10].
• GLP-2 increased the mean metaphase arrests/crypt in both the jejunum and ileum (P < 0.001) [9].
• Giving dams GLP-2 or DEX during pregnancy and lactation reduced lipid uptake in the offspring, and this persisted for at least 1 mon [11].

Anatomical context of Mcpt10

• Mammalian proglucagon, which is synthesized in the neuroendocrine L-cells of the intestine and the alpha-cells of the pancreas, contains within its structure the sequences of glucagon and two glucagon-like peptides (GLP-I and GLP-II) flanked at their amino and carboxyl termini by dibasic residues [12].
• Hence GLP-2 may be therapeutically useful in diseases characterised by injury or dysfunction of the gastrointestinal epithelium [1].
• This shows that SEN improve the intestinotrophic response to exogenous GLP-2, possibly by stimulating enterocyte proliferation and differentiation [13].
• Glucagon-like peptide-2 (GLP-2) is secreted by enteroendocrine cells in the small and large intestines and exerts intestinotropic effects in the gastrointestinal mucosal epithelium of the adult rodent [14].
• A possible role for GLUT2 transiently expressed in the rat jejunal brush-border membrane (BBM) under the influence of glucagon-like peptide 2 (GLP-2) was investigated using in vivo perfusion of the intestinal lumen as well as isolation of membrane proteins and immunohistochemistry [15].

Associations of Mcpt10 with chemical compounds

• Perfusion of the intestinal lumen with 50 mM D-glucose or vascular infusion of 800 pM GLP-2 for 1 h increased the expression of GLUT2 in the BBM [15].
• A 1 h vascular infusion of GLP-2 in vivo doubled the rate of fructose absorption and this increase could be blocked by luminal phloretin [15].
• Treatment of suckling rats with GLP-2 plus dexamethasone increases the ileal uptake of fatty acids in later life [3].
• We previously reported cloning of cDNAs which encode two granzyme-like serine proteinases (GLP I and GLP II) from rat duodenum [10].
• Earlier, we found elevated levels of endogenous GLP-2 in untreated streptozotocin diabetic rats associated with marked intestinal growth [16].

Physical interactions of Mcpt10

• It is, however, unknown whether oxyntomodulin and GLP-2 elicit a biological response by interacting with the GLP-1 receptor [17].
• These findings suggest that the GLP-2R may be coupled to activation of mitogenic signaling in heterologous cell types independent of PKA via as yet unidentified downstream mediators of GLP-2 action in vivo [7].
• Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo [18].

Regulatory relationships of Mcpt10

• These results indicate that GLP-2 is able to induce trafficking of SGLT-1 from an intracellular pool into the BBM within 60 min and that phosphoinositol 3-kinase may well be involved in the intracellular signaling pathway in this response [18].

Other interactions of Mcpt10

• However, BFA significantly reduced the upregulation induced by lumenal glucose and vascular GIP and blocked the stimulation produced by vascular GLP-2 [19].
• The actions of GLP-2 are mediated by the GLP-2 receptor, a new member of the G protein-coupled receptor superfamily [14].
• Glucagon-like peptide-2 (GLP-2) is a potent intestinotrophic/satiety hormone that acts through a G protein-coupled receptor [20].
• GLP-2 does not adversely affect the diurnal expression rhythm of SGLT1 and appears to increase membrane expression of the protein [21].
• GLP-2 did not affect intestinal somatostatin release [22].

Analytical, diagnostic and therapeutic context of Mcpt10

• Chromatographic analyses of cell extracts utilizing specific radioimmunoassays to chemically synthesized peptides demonstrate the liberation of intact glucagon, glicentin, GLP-I(1-37), GLP-I(7-37), GLP-II, and an intervening peptide amidated at its carboxyl terminus [23].
• Glucagon-like peptide-2 (GLP-2) has recently been identified as a stimulator of intestinal epithelial growth, prompting the development of RIA and HPLC methodologies to study this peptide in more detail [24].
• GLP-I-(1-37), GLP-I-(7-37), GLP-II, IP-II, and IP-II amide coeluted with their respective synthetic peptide standards on gel filtration and ion exchange chromatography [25].
• Quantification of these changes using Western blotting of biotinylated surface-exposed protein showed a doubling of the expression of GLUT2 in the BBM, but the effects of glucose and GLP-2 were not additive [15].
• Herein, we investigate the effects of GLP-2 in a total parenteral nutrition (TPN)-supported model of experimental short bowel syndrome [2].

References