title: Heat shock protein 72 protects insulin-secreting beta cells from lipopolysaccharide-induced endoplasmic reticulum stress.
abstract: OBJECTIVE
  Hyperthermia-induced activation of stress response proteins allows cells to withstand metabolic insults. In this study we set out to determine whether insulin secretion by pancreatic beta cells was affected by the acute inflammatory response, systemic inflammation-induced hyperglycaemia, and whole-body hyperthermia. Given that systemic-inflammation induces ER stress, we further examined whether hyperthermia can attenuate the extent of LPS-induced ER stress.
  
  
  METHODS
  Rats were randomised and divided into three treatment groups. Control rats received a 0.9% NaCl solution. Rats in the lipopolysaccharide (LPS) group received 7.5 mg of LPS/kg. Rats in the whole-body hyperthermia (WBH) + LPS group were exposed to 42 degrees C for 15 min, followed by injection with 7.5 mg of LPS/kg after 48 h. Glucose-potentiated insulin release and extent of ER stress were measured in beta cells.
  
  
  RESULTS
  LPS inhibited glucose-induced insulin release from islet cells and induced the expression of Bip/GRP78, XBP-1, and CHOP transcripts. The inhibition of glucose-induced insulin release and induction of ER stress proteins by LPS was attenuated by WBH.
  
  
  CONCLUSIONS
  Our findings suggest that LPS-induced systemic inflammation decreased insulin release due to the effects of ER stress proteins on insulin secretion. Furthermore, the induction of ER stress proteins was prevented by pretreating rats with WBH. This may suggest that inhibiting the induction of ER stress proteins through WBH can restore insulin release in various disease states.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan. saku@med.oita-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shingu
authors.forename: Shigekiyo
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Akira
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Asai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D005334:Fever / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000502:physiology*; D006979:Hyperthermia, Induced; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D050884:HSP72 Heat-Shock Proteins; D007328:Insulin; D008070:Lipopolysaccharides