Linked Life Data

20975661

Source:http://linkedlifedata.com/resource/pubmed/id/20975661

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-2-1
pubmed:abstractText
Intestinal ischemia/reperfusion (I/R) causes mucosal barrier damage and bacterial translocation (BT), leading to septic complications. Previous in vitro studies showed that activation of sodium/glucose transporter 1 (SGLT1) prevented the epithelial apoptosis and permeability rise induced by microbial products. Our aim was to investigate whether luminal glucose uptake by SGLT1 protects against ischemia-induced epithelial cell death and barrier dysfunction, and to explore the glucose-mediated cellular survival pathways in vivo. Rat jejunum was luminally instilled with either vehicle, a pancaspase inhibitor ZVAD, or glucose prior to I/R challenge (occlusion of the superior mesenteric artery for 20?min and reperfusion for 60?min). Histopathology and apoptosis in the jejunum were examined by TUNEL staining and caspase-3 cleavage. Intestinal permeability was evaluated using in vivo assays measuring luminal-to-blood passage of fluorescein-dextran and portal drainage of enterally administered gadodiamide by magnetic resonance imaging. BT was determined by culturing liver and spleen homogenates. Immunofluorescent analysis and kinase assay were used to study PI3K/Akt signaling pathways. Intestinal I/R caused enterocyte apoptosis and villous destruction. Intestinal infusion with ZVAD decreased the I/R-triggered gut permeability rise and BT, suggesting that the barrier damage was partly dependent on cell apoptosis. Enteral instillation of glucose attenuated the epithelial apoptosis, barrier damage, and mucosal inflammation caused by I/R. Phloridzin (a SGLT1 inhibitor) reduced the protective effect of glucose in a dose-dependent manner. Enteral glucose increased the mucosal Akt kinase activity as evidenced by the augmented phosphorylation of exogenous GSK3. Enhanced membrane translocation and phosphorylation of Akt in epithelial cells were associated with elevated phosphorylation of mTOR, Bad, and FoxO1/3a following glucose uptake. Inhibition of PI3K/Akt signaling by LY294002 and wortmannin partially blocked the glucose-mediated rescue of cell apoptosis and barrier damage. In conclusion, SGLT1 glucose uptake alleviated I/R-induced barrier dysfunction and BT, partly by inhibiting epithelial apoptosis via activation of PI3K/Akt signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1530-0307
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
294-309
pubmed:meshHeading
pubmed-meshheading:20975661-Animals, pubmed-meshheading:20975661-Apoptosis, pubmed-meshheading:20975661-Caspase 3, pubmed-meshheading:20975661-Fluorescent Antibody Technique, pubmed-meshheading:20975661-Gadolinium DTPA, pubmed-meshheading:20975661-Glucose, pubmed-meshheading:20975661-In Situ Nick-End Labeling, pubmed-meshheading:20975661-Intestinal Mucosa, pubmed-meshheading:20975661-Jejunum, pubmed-meshheading:20975661-Magnetic Resonance Imaging, pubmed-meshheading:20975661-Male, pubmed-meshheading:20975661-Oncogene Protein v-akt, pubmed-meshheading:20975661-Permeability, pubmed-meshheading:20975661-Phlorhizin, pubmed-meshheading:20975661-Phosphatidylinositol 3-Kinases, pubmed-meshheading:20975661-Phosphorylation, pubmed-meshheading:20975661-Rats, pubmed-meshheading:20975661-Rats, Wistar, pubmed-meshheading:20975661-Reperfusion Injury, pubmed-meshheading:20975661-Signal Transduction, pubmed-meshheading:20975661-Sodium-Glucose Transporter 1
pubmed:year
2011
pubmed:articleTitle
Anti-apoptotic PI3K/Akt signaling by sodium/glucose transporter 1 reduces epithelial barrier damage and bacterial translocation in intestinal ischemia.
pubmed:affiliation
Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't