Abstract | OBJECTIVE: DESIGN: Controlled animal study. SETTING: University research laboratory. SUBJECTS: One hundred fifty-four BALB/c mice (8-12 wks of age). INTERVENTIONS: MEASUREMENTS AND MAIN RESULTS: Septic mice were markedly hyperinsulinemic with apparently normal blood glucose levels in the fasted state, suggesting they are insulin-resistant. In fact, glucose clearance in response to insulin was markedly impaired in septic mice. They had impaired GLUT4 membrane translocation resulting from impaired insulin signaling as indicated by the decreased amount of insulin receptor substrate protein and the reduced activation of phosphatidylinositol 3-kinase and Akt. Interestingly, injection of nuclear factor-kappaB decoy oligodeoxynucleotide into the skeletal muscle dramatically improved all of the changes, including glucose clearance and insulin signaling. We also found that the Cbl-associated protein to TC10 pathway, another pathway regulating GLUT4 translocation, was up-regulated in septic mice in a nuclear factor-kappaB-dependent manner. This pathway may be one of the compensatory mechanisms to translocate GLUT4 because silencing of the individual components of the pathway with small interfering RNAs further reduced GLUT4 translocation in muscles of septic mice. CONCLUSIONS:
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Authors | Naoyuki Matsuda, Seiji Yamamoto, Hiroki Yokoo, Kazuyuki Tobe, Yuichi Hattori |
Journal | Critical care medicine
(Crit Care Med)
Vol. 37
Issue 10
Pg. 2791-9
(Oct 2009)
ISSN: 1530-0293 [Electronic] United States |
PMID | 19707125
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Blood Glucose
- Glucose Transporter Type 4
- NF-kappaB decoy
- Oligodeoxyribonucleotides
- RNA, Small Interfering
- Slc2a4 protein, mouse
- Phosphatidylinositol 3-Kinases
- Oncogene Protein v-akt
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Topics |
- Animals
- Blood Glucose
(metabolism)
- Disease Models, Animal
- Glucose Transporter Type 4
(genetics)
- Hyperinsulinism
(genetics)
- Insulin Resistance
(genetics)
- Intestinal Perforation
(genetics)
- Male
- Mice
- Mice, Inbred BALB C
- Muscle, Skeletal
(metabolism)
- Oligodeoxyribonucleotides
(genetics)
- Oncogene Protein v-akt
(physiology)
- Phosphatidylinositol 3-Kinases
(physiology)
- RNA, Small Interfering
(genetics)
- Sepsis
(genetics)
- Signal Transduction
(genetics)
- Transfection
- Translocation, Genetic
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