Hyperthermia with mild electrical stimulation protects pancreatic β-cells from cell stresses and apoptosis.
Hyperthermia with mild electrical stimulation protects pancreatic β-cells from cell stresses and apoptosis.
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作者：
Kondo T;Sasaki K;Matsuyama R;Morino-Koga S;Adachi H;Suico MA;Kawashima J;Motoshima H;Furukawa N;Kai H;Araki E
诱导热休克蛋白（HSP） 72改善糖尿病模型小鼠的代谢谱。然而，其对胰腺β细胞的影响尚不清楚。本研究探讨HSP72诱导是否能减少β-细胞应激信号传导和凋亡，并保持β-细胞质量。对MIN6细胞和db/db小鼠进行假处理或热休克(HS) +轻度电刺激（HS+MES）诱导HSP72。几个细胞标志物，代谢参数和β细胞质量进行了评估。HS+MES处理或HSP72过表达增加了HSP72蛋白水平，降低了肿瘤坏死因子(TNF)-α -诱导的Jun nh2末端激酶（JNK）磷酸化、内质网（ER）应激和促凋亡信号。在db/db小鼠中，HS+MES治疗12周可显著改善胰岛素敏感性和葡萄糖稳态。葡萄糖刺激后，体内胰岛素分泌显著增加。与假治疗相比，HS+ mess治疗小鼠胰岛HSP72、胰岛素、胰十二指肠同源盒-1、GLUT2和胰岛素受体底物-2水平上调，而JNK磷酸化、叉头盒O-1类核易位和核因子-κB p65水平降低。凋亡信号、内质网应激和氧化应激标志物减弱。因此，HS+MES处理诱导HSP72通过减弱JNK激活和细胞应激来保护β-细胞免于凋亡。HS+MES联合治疗可保持胰腺β细胞体积，改善糖尿病患者的葡萄糖稳态。
Induction of heat shock protein (HSP) 72 improves metabolic profiles in diabetic model mice. However, its effect on pancreatic β-cells is not known. The current study investigated whether HSP72 induction can reduce β-cell stress signaling and apoptosis and preserve β-cell mass. MIN6 cells and db/db mice were sham-treated or treated with heat shock (HS) and mild electrical stimulation (MES) (HS+MES) to induce HSP72. Several cellular markers, metabolic parameters, and β-cell mass were evaluated. HS+MES treatment or HSP72 overexpression increased HSP72 protein levels and decreased tumor necrosis factor (TNF)-α–induced Jun NH2-terminal kinase (JNK) phosphorylation, endoplasmic reticulum (ER) stress, and proapoptotic signal in MIN6 cells. In db/db mice, HS+MES treatment for 12 weeks significantly improved insulin sensitivity and glucose homeostasis. Upon glucose challenge, a significant increase in insulin secretion was observed in vivo. Compared with sham treatment, levels of HSP72, insulin, pancreatic duodenal homeobox-1, GLUT2, and insulin receptor substrate-2 were upregulated in the pancreatic islets of HS+MES-treated mice, whereas JNK phosphorylation, nuclear translocation of forkhead box class O-1, and nuclear factor-κB p65 were reduced. Apoptotic signals, ER stress, and oxidative stress markers were attenuated. Thus, HSP72 induction by HS+MES treatment protects β-cells from apoptosis by attenuating JNK activation and cell stresses. HS+MES combination therapy may preserve pancreatic β-cell volume to ameliorate glucose homeostasis in diabetes.
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影响因子：
7.7
作者：
Kawamori, D;Kajimoto, Y;Hori, M
通讯作者：
Hori, M
影响因子：
3.2
作者：
Araki, E;Oyadomari, S;Mori, M
通讯作者：
Mori, M
DOI：
10.1073/pnas.0705799105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Chung, Jason;Nguyen, Anh-Khoi;Febbraio, Mark A.
通讯作者：
Febbraio, Mark A.
影响因子：
7.7
作者：
Kurucz, I;Morva, A;Koranyi, L
通讯作者：
Koranyi, L
影响因子：
4.9
作者：
Hotamisligil, G. S.
通讯作者：
Hotamisligil, G. S.