Tumor necrosis factor-α mediates hyperglycemia-augmented gut barrier dysfunction in endotoxemia

Satoshi Yajima, Hiroshi Morisaki, Ryohei Serita, Takeshi Suzuki, Nobuyuki Katori, Takashi Asahara, Koji Nomoto, Fujio Kobayashi, Akitoshi Ishizaka, Junzo Takeda

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

OBJECTIVE:: To examine whether hyperglycemia would augment gut barrier dysfunction and inflammatory responses in endotoxemic rats, and simultaneously to clarify the roles of tumor necrosis factor (TNF)-α in alterations of gut mucosal permeability associated with hyperglycemia. DESIGN:: Prospective randomized animal study. SETTING:: University research laboratory. SUBJECTS:: Male Wistar rats treated with lipopolysaccharide (LPS) injection. 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-α using an inhibitor of TNF-α 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-α 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-α 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-α mediates such mucosal dysfunction of gut in endotoxemia.

Original languageEnglish
Pages (from-to)1024-1030
Number of pages7
JournalCritical Care Medicine
Volume37
Issue number3
DOIs
Publication statusPublished - 2009 Mar

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Endotoxemia
Hyperglycemia
Tumor Necrosis Factor-alpha
Lipopolysaccharides
Permeability
Insulin
Dextrans
Blood Glucose
Fluorescence
Lymph Nodes
Biphasic Insulins
Bacterial Translocation
Glucose
Injections
Hyperinsulinism
Sodium Chloride
Wistar Rats
Cytokines
Bacteria
Acids

Keywords

  • Endotoxin
  • Gut mucosal permeability
  • Hyperglycemia
  • Insulin
  • TNF-α converting enzyme

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Tumor necrosis factor-α mediates hyperglycemia-augmented gut barrier dysfunction in endotoxemia. / Yajima, Satoshi; Morisaki, Hiroshi; Serita, Ryohei; Suzuki, Takeshi; Katori, Nobuyuki; Asahara, Takashi; Nomoto, Koji; Kobayashi, Fujio; Ishizaka, Akitoshi; Takeda, Junzo.

In: Critical Care Medicine, Vol. 37, No. 3, 03.2009, p. 1024-1030.

Research output: Contribution to journalArticle

Yajima, S, Morisaki, H, Serita, R, Suzuki, T, Katori, N, Asahara, T, Nomoto, K, Kobayashi, F, Ishizaka, A & Takeda, J 2009, 'Tumor necrosis factor-α mediates hyperglycemia-augmented gut barrier dysfunction in endotoxemia', Critical Care Medicine, vol. 37, no. 3, pp. 1024-1030. https://doi.org/10.1097/CCM.0b013e31819b53b6
Yajima, Satoshi ; Morisaki, Hiroshi ; Serita, Ryohei ; Suzuki, Takeshi ; Katori, Nobuyuki ; Asahara, Takashi ; Nomoto, Koji ; Kobayashi, Fujio ; Ishizaka, Akitoshi ; Takeda, Junzo. / Tumor necrosis factor-α mediates hyperglycemia-augmented gut barrier dysfunction in endotoxemia. In: Critical Care Medicine. 2009 ; Vol. 37, No. 3. pp. 1024-1030.
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