Abstract | OBJECTIVE: DESIGN: Prospective randomized animal study. SETTING: University research laboratory. SUBJECTS: INTERVENTIONS: After LPS injection (4 mg/kg), rats were randomly allocated into group S (n = 6), group G (n = 7), or group GI (n = 8) with continuous infusion of different fluid solutions: normal saline, 40% glucose or 10% glucose mixed with insulin, respectively. Blood glucose, insulin, and proinflammatory cytokines, accompanied by gut mucosal permeability using an in situ loop preparation of gut with fluorescence isothiocyanate-conjugated dextran, were measured. Bacterial growth or alterations in mesenteric lymph nodes and cecal contents were also assessed. We further determined the roles of TNF-alpha using an inhibitor of TNF-alpha converting enzyme in gut barrier dysfunction under the same experimental settings. MEASUREMENTS AND MAIN RESULTS:
Hyperglycemia over 400 mg/dL was achieved and kept in group G during the study period whereas normoglycemia was preserved in group S and GI, the latter of which showed the similar extent of hyperinsulinemia to group G. Plasma concentrations of fluorescence-labeled dextran and TNF-alpha in group G were significantly higher vs. group S and GI, and the number of bacteria found in mesenteric lymph nodes in group G was greater compared with group S. Intestinal environments including microflora and organic acids were not altered by blood glucose or insulin level. Inhibiting conversion of membrane-bound to soluble type of TNF-alpha restored gut mucosal permeability augmented by hyperglycemia. CONCLUSIONS: These findings indicate that hyperglycemia deteriorates LPS-elicited gut barrier dysfunction and bacterial translocation independently of plasma insulin level, and that TNF-alpha mediates such mucosal dysfunction of gut in endotoxemia.
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Authors | Satoshi Yajima, Hiroshi Morisaki, Ryohei Serita, Takeshi Suzuki, Nobuyuki Katori, Takashi Asahara, Koji Nomoto, Fujio Kobayashi, Akitoshi Ishizaka, Junzo Takeda |
Journal | Critical care medicine
(Crit Care Med)
Vol. 37
Issue 3
Pg. 1024-30
(Mar 2009)
ISSN: 1530-0293 [Electronic] United States |
PMID | 19237913
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Tumor Necrosis Factor-alpha
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Topics |
- Animals
- Endotoxemia
(blood, complications, immunology, metabolism, physiopathology)
- Hyperglycemia
(blood, complications, immunology, metabolism, physiopathology)
- Intestinal Mucosa
(metabolism)
- Intestines
(microbiology)
- Male
- Permeability
- Rats
- Rats, Wistar
- Tumor Necrosis Factor-alpha
(physiology)
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