The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis

Kouris, George J; Liu, Qiang; Rossi, Heather L.; Djuricin, Goldie; Gattuso, Paulo; Nathan, Catherine; Weinstein, Robert A.; Prinz, Richard A.

doi:10.1016/s0002-9610(01)00635-3

Cited by 63 publications

(45 citation statements)

References 15 publications

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“…Several experimental studies examining the role of GLP-2 to treat diseases characterized by intestinal inflammation (Boushey et al, 1999;Alavi et al, 2000;Kouris et al, 2001) suggest a role for GLP-2 in ameliorating the severity of inflammation, perhaps indirectly by enhancing the integrity of the intestinal barrier. In this study, GLP-2 treatment of stressed mice reduced the number of mononuclear cells recruited to the mucosa, perhaps by limiting immune stimulation via enhanced barrier function.…”

Section: Discussionmentioning

confidence: 99%

Stress Impairs Murine Intestinal Barrier Function: Improvement by Glucagon-Like Peptide-2

Cameron

Perdue

2005

J Pharmacol Exp Ther

104

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Stress-induced intestinal barrier dysfunction may be involved in chronic intestinal disorders. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic growth hormone that can rapidly improve intestinal epithelial barrier function. Here, we investigated whether mouse intestine is responsive to chronic psychological stress and whether pretreatment with GLP-2 can ameliorate stress-induced changes. Mice were subjected to water avoidance stress (WAS; 1 h/day for 10 days) with GLP-2 or saline administered 4 h before each WAS session. After the final stress period, the intestine was removed for assessment of physiological/morphological changes. Compared with controls (sham-stressed mice), stressed mice demonstrated enhanced ion secretion and permeability in the jejunum, ileum, and colon. In addition, increased numbers of bacteria were observed adhering to and/or penetrating the epithelium, associated with infiltration of mononuclear cells into the mucosa. GLP-2 treatment improved intestinal barrier function in stressed mice and ameliorated other aspects of impaired host defense. Our study extends previous findings in rats of stress-induced intestinal dysfunction and provides insights into potential novel therapeutics.

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Section: Discussionmentioning

confidence: 99%

Stress Impairs Murine Intestinal Barrier Function: Improvement by Glucagon-Like Peptide-2

Cameron

Perdue

2005

J Pharmacol Exp Ther

104

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“…Although GLP-2 does not parallel the effects of enteral nutrition on enzyme activities in premature newborn pigs, the positive effects of GLP-2 in maintaining enzyme activity, coupled with increased small intestine mass (11) and the demonstrated ability of GLP-2 to decrease intestinal permeability (24) and improve nutrient absorption (25), suggests that GLP-2 could be of great clinical significance in the treatment of the immature intestine.…”

Section: Glp-2 and Brush-border Hydrolases In Premature Pigletsmentioning

confidence: 99%

Glucagon-Like Peptide 2 Enhances Maltase-Glucoamylase and Sucrase-Isomaltase Gene Expression and Activity in Parenterally Fed Premature Neonatal Piglets

PETERSEN¹

2002

Pediatric Research

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Exogenous glucagon-like peptide 2 (GLP-2) mimics the stimulatory effect of enteral nutrition on intestinal mucosal growth in preterm neonatal pigs. Little is known about its effects on small intestinal function. In this study, we investigated whether the trophic actions of GLP-2 and enteral nutrition are paralleled by effects on small intestinal function. Cesarean-delivered piglets (92% of gestation) were given either a parenteral nutrient infusion [total parenteral nutrition (TPN), n ϭ 7], TPN ϩ human GLP-2 (25 nmol/kg/d, n ϭ 8), or enteral nutrition (ENT, n ϭ 6) for 6 d. Gene expression (mRNA) and activities of lactase phlorizin hydrolase (LPH), maltase-glucoamylase (MGA), sucrase-isomaltase (SI), aminopeptidase N (ApN), and A (ApA) and dipeptidyl peptidase IV (DPP IV) were measured. Both GLP-2 and enteral nutrition increased mucosal weight (ϩ30 -40%, p Ͻ 0.05) relative to TPN. GLP-2 stimulated jejunal MGA and SI mRNA abundance and activity levels but did not change LPH in parenterally fed pigs (p Ͻ 0.05). Enteral nutrition decreased jejunal LPH and MGA mRNA abundance and activity and increased ileal ApN, ApA, and DPP IV activities relative to TPN (p Ͻ 0.05). We conclude that GLP-2 and enteral nutrition exert different effects on intestinal enzyme function despite similar effects on intestinal growth. In addition, the effects of GLP-2 on intestinal function in these parenterally fed, premature neonatal pigs differed from those previously reported for similarly fed term neonates. (Pediatr Res 52: 498-503, 2002) Abbreviations ApN, aminopeptidase N ApA, aminopeptidase A AS, antisense BB, brush border DEPC, diethylpyrocarbonate DPP IV, dipeptidyl peptidase IV ENT, enteral nutrition GIT, gastrointestinal tract GLP-2, glucagon-like peptide 2 LPH, lactase-phlorizin hydrolase MGA, maltase-glucoamylase S, sense SI, sucrase-isomaltase TPN, total parenteral nutrition TPN is frequently administered to premature infants unable to tolerate enteral nutrition. TPN provides systemic energy and nutrients but has been associated with intestinal atrophy, abnormal BB hydrolase activities, and reduced circulating GLP-2 concentrations (1-5). GLP-2 is a 33-amino acid peptide released from the specific post-translational cleaving of the proglucagon gene in the enteroendocrine L cells of the small intestine. This gut peptide stimulates significant mucosal proliferation (6), hexose transport (7), and duodenal hydrolase activity (8), seemingly via a specific G-protein-coupled receptor present in the small intestine (9). GLP-2 is released in response to enteral nutrient intake (5, 10) and is thought to mediate the response of the small intestine to enteral nutrients (11). Recently, however, it has been shown that GLP-2 stimulates intestinal growth by inhibiting apoptosis and proteolysis, and enteral nutrition also inhibits apoptosis but furthermore increases protein synthesis and cell proliferation (11). Thus, despite the similarity in the extent of small intestinal mucosal growth induced by GLP-2 and enteral nutrition, the mechanisms inv...

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“…This indicates that GLP-2 exerts its effects via neuronal and endocrine cells instead of enterocytes and that systemic effects of GLP-2 are indirectly mediated by secondary signals (21). The protective effect of GLP-2 on the GIS is associated with its ability to increase barrier function and decrease gastrointestinal permeability (22).…”

Section: Discussionmentioning

confidence: 99%

Effects of glucagon-like peptide-2 on bacterial translocation in rat models of colitis

Halaçlar¹,

A²,

Ac³

et al. 2012

Turk J Gastroenterol

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The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis

Cited by 63 publications

References 15 publications

Stress Impairs Murine Intestinal Barrier Function: Improvement by Glucagon-Like Peptide-2

Stress Impairs Murine Intestinal Barrier Function: Improvement by Glucagon-Like Peptide-2

Glucagon-Like Peptide 2 Enhances Maltase-Glucoamylase and Sucrase-Isomaltase Gene Expression and Activity in Parenterally Fed Premature Neonatal Piglets

Effects of glucagon-like peptide-2 on bacterial translocation in rat models of colitis

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