Heat shock protein 72 protects insulin-secreting beta cells from lipopolysaccharide-induced endoplasmic reticulum stress.
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.
Hagiwara
Satoshi
S
Department of Anaesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan. saku@med.oita-u.ac.jp
Iwasaka
Hideo
H
Shingu
Chihiro
C
Matsumoto
Shigekiyo
S
Hasegawa
Akira
A
Asai
Nobuhiko
N
Noguchi
Takayuki
T
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
D050884:HSP72 Heat-Shock Proteins; D007328:Insulin; D008070:Lipopolysaccharides