title: Selective decontamination of the digestive tract ameliorates severe burn-induced insulin resistance in rats.
abstract: BACKGROUND
  Severe burns often initiate the prevalence of hyperglycemia and insulin resistance, significantly contributing to adverse clinical outcomes. However, there are limited treatment options. This study was designed to investigate the role and the underlying mechanisms of oral antibiotics to selectively decontaminate the digestive tract (SDD) on burn-induced insulin resistance.
  
  
  METHODS
  Rats were subjected to 40% of total body surface area full-thickness burn or sham operation with or without SDD treatment. Translocation of FITC-labeled LPS was measured at 4h after burn. Furthermore, the effect of SDD on post-burn quantity of gram-negative bacteria in gut was investigated. Serum or muscle LPS and proinflammatory cytokines were measured. Intraperitoneal glucose tolerance test and insulin tolerance test were used to determine the status of systemic insulin resistance. Furthermore, intracellular insulin signaling (IRS-1 and Akt) and proinflammatory related kinases (JNK and IKKβ) were assessed by western blot.
  
  
  RESULTS
  Burn increased the translocation of LPS from gut 4h after injury. SDD treatment effectively inhibited post-burn overgrowth of gram-negative enteric bacilli in gut. In addition, severe burns caused significant increases in the LPS and proinflammatory cytokines levels, activation of proinflammatory related kinases, and systemic insulin resistance as well. But SDD treatment could significantly attenuate burn-induced insulin resistance and improve the whole-body responsiveness to insulin, which was associated with the inhibition of gut-derived LPS, cytokines, proinflammatory related kinases JNK and IKKβ, as well as activation of IRS-1 and Akt.
  
  
  CONCLUSIONS
  SDD appeared to have an effect on proinflammatory signaling cascades and further reduced severe burn-induced insulin resistance.
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi'an, China; Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medical Education, Fourth Military Medical University, Xi'an, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi'an, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xuekang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Huayu
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi'an, China; Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi'an, China; Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yangfan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: xjburns@163.com.
authors.forename: Dahai
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi'an, China; Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, China. Electronic address: fgao@fmmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002056:Burns / Q000378:metabolism* / Q000382:microbiology; D003091:Colistin / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D005437:Flucytosine / Q000494:pharmacology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism; D005951:Glucose Tolerance Test; D051550:I-kappa B Kinase / Q000187:drug effects / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000187:drug effects / Q000378:metabolism; D007333:Insulin Resistance; D008070:Lipopolysaccharides / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010539:Permeability; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D016207:Cytokines; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D008070:Lipopolysaccharides; D005437:Flucytosine; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D048670:MAP Kinase Kinase 4; D014031:Tobramycin; D003091:Colistin
keywords: Burn; Insulin resistance; LPS; Proinflammatory cytokine; SDD