Department of Anaesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan.
Int J Hyperthermia. 2009 Dec;25(8):626-33. doi: 10.3109/02656730903279102.
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.
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.
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.
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.
热应激诱导的应激反应蛋白的激活使细胞能够耐受代谢损伤。在这项研究中，我们旨在确定胰腺β细胞的胰岛素分泌是否受到急性炎症反应、全身炎症诱导的高血糖和全身发热的影响。鉴于全身炎症会引起内质网应激，我们进一步研究了全身发热是否可以减轻 LPS 诱导的内质网应激的程度。
将大鼠随机分为三组。对照组大鼠给予 0.9%氯化钠溶液。脂多糖（LPS）组大鼠给予 7.5mg/kg LPS。全身发热（WBH）+LPS 组大鼠暴露于 42°C 15min，48h 后给予 7.5mg/kg LPS 注射。测量β细胞中葡萄糖增强的胰岛素释放和内质网应激的程度。
LPS 抑制胰岛细胞的葡萄糖诱导胰岛素释放，并诱导 Bip/GRP78、XBP-1 和 CHOP 转录物的表达。WBH 减轻了 LPS 对葡萄糖诱导胰岛素释放和内质网应激蛋白的抑制作用。
我们的研究结果表明，LPS 诱导的全身炎症通过内质网应激蛋白对胰岛素分泌的影响降低了胰岛素释放。此外，用 WBH 预处理大鼠可防止内质网应激蛋白的诱导。这可能表明，通过 WBH 抑制内质网应激蛋白的诱导可以恢复各种疾病状态下的胰岛素释放。
