title: Acute insulin resistance mediated by advanced glycation endproducts in severely burned rats.
abstract: OBJECTIVE
  Hyperglycemia often occurs in severe burns; however, the underlying mechanisms and importance of managing postburn hyperglycemia are not well recognized. This study was designed to investigate the dynamic changes of postburn hyperglycemia and the underlying mechanisms and to evaluate whether early glycemic control is beneficial in severe burns.
  
  
  METHODS
  Prospective, randomized experimental study.
  
  
  METHODS
  Animal research laboratory.
  
  
  METHODS
  Sprague-Dawley rats.
  
  
  METHODS
  Anesthetized rats were subjected to a full-thickness burn injury comprising 40% of the total body surface area and were randomized to receive vehicle, insulin, and a soluble form of receptor for advanced glycation endproducts treatments. An in vitro study was performed on cultured H9C2 cells subjected to vehicle or carboxymethyllysine treatment.
  
  
  RESULTS
  We found that blood glucose change presented a distinct pattern with two occurrences of hyperglycemia at 0.5- and 3-hour postburn, respectively. Acute insulin resistance evidenced by impaired insulin signaling and glucose uptake occurred at 3-hour postburn, which was associated with the second hyperglycemia and positively correlated with mortality. Mechanistically, we found that serum carboxymethyllysine, a dominant species of advanced glycation endproducts, increased within 1-hour postburn, preceding the occurrence of insulin resistance. More importantly, treatment of animals with soluble form of receptor for advanced glycation endproducts, blockade of advanced glycation endproducts signaling, alleviated severe burn-induced insulin resistance. In addition, early hyperglycemic control with insulin not only reduced serum carboxymethyllysine but also blunted postburn insulin resistance and reduced mortality.
  
  
  CONCLUSIONS
  These findings suggest that severe burn-induced insulin resistance is partly at least mediated by serum advanced glycation endproducts and positively correlated with mortality. Early glycemic control with insulin or inhibition of advanced glycation endproducts with soluble form of receptor for advanced glycation endproducts ameliorates postburn insulin resistance.
authors.affiliation: 1Department of Physiology, School of Basic Medical Sciences, The Fourth Military Medical University, Xi'an, China. 2Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. 3Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. 4Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. 5Institute of Molecular Medicine, Peking University, Beijing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Cai
authors.forename: Lele
authors.initials: L
authors.lastname: Ji
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Cao
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Dahai
authors.initials: D
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.forename: Ruiping
authors.initials: R
authors.lastname: Xiao
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002056:Burns / Q000150:complications* / Q000378:metabolism / Q000401:mortality; D002460:Cell Line; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy / Q000209:etiology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D053208:Kaplan-Meier Estimate; D008239:Lysine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007328:Insulin; C048496:N(6)-carboxymethyllysine; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D008239:Lysine