GLP-2 Acutely Prevents Endotoxin-Related Increased Intestinal Paracellular Permeability in Rats.
Dig Dis Sci
; 65(9): 2605-2618, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32006214
ABSTRACT
BACKGROUND:
Circulating endotoxin (lipopolysaccharide, LPS) increases the gut paracellular permeability. We hypothesized that glucagon-like peptide-2 (GLP-2) acutely reduces LPS-related increased intestinal paracellular permeability by a mechanism unrelated to its intestinotrophic effect.METHODS:
We assessed small intestinal paracellular permeability in vivo by measuring the appearance of intraduodenally perfused FITC-dextran 4000 (FD4) into the portal vein (PV) in rats 1-24 h after LPS treatment (5 mg/kg, ip). We also examined the effect of a stable GLP-2 analog teduglutide (TDG) on FD4 permeability.RESULTS:
FD4 movement into the PV was increased 6 h, but not 1 or 3 h after LPS treatment, with increased PV GLP-2 levels and increased mRNA expressions of proinflammatory cytokines and proglucagon in the ileal mucosa. Co-treatment with a GLP-2 receptor antagonist enhanced PV FD4 concentrations. PV FD4 concentrations 24 h after LPS were higher than FD4 concentrations 6 h after LPS, reduced by exogenous GLP-2 treatment given 6 or 12 h after LPS treatment. FD4 uptake measured 6 h after LPS was reduced by TDG 3 or 6 h after LPS treatment. TDG-associated reduced FD4 uptake was reversed by the VPAC1 antagonist PG97-269 or L-NAME, not by EGF or IGF1 receptor inhibitors.CONCLUSIONS:
Systemic LPS releases endogenous GLP-2, reducing LPS-related increased permeability. The therapeutic window of exogenous GLP-2 administration is at minimum within 6-12 h after LPS treatment. Exogenous GLP-2 treatment is of value in the prevention of increased paracellular permeability associated with endotoxemia.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Endotoxemia
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Peptídeo 2 Semelhante ao Glucagon
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Receptor do Peptídeo Semelhante ao Glucagon 2
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Absorção Intestinal
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Intestino Delgado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Dig Dis Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos