Mild electrical stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling.
Mild electrical stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling.
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DOI：
10.1371/journal.pone.0004068
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Kai, Hirofumi
中科院分区：
文献类型：
--
作者：
Morino, Saori;Kondo, Tatsuya;Sasaki, Kazunari;Adachi, Hironori;Suico, Mary Ann;Sekimoto, Erika;Matsuda, Tomoko;Shuto, Tsuyoshi;Araki, Eiichi;Kai, Hirofumi
低强度电流(或轻度电刺激；MES)影响信号转导，激活磷脂酰肌醇-3激酶(PI3K)/Akt通路。由于胰岛素抵抗的特征是胰岛素刺激的PI3K介导的Akt激活显著减少，我们询问MES是否可以增加Akt的磷酸化并改善胰岛素抵抗。此外，此前也有报道称热休克蛋白72(HSP72)可以缓解高血糖。因此，我们将MES与热休克(HS)相结合应用于胰岛素抵抗的体外和体内模型。在这里，我们发现在5V(0.1ms脉冲宽度)的MES和42°C的HS联合作用10分钟，在维持在高糖介质中的HepG2细胞中，胰岛素受体底物(IRS)和Akt等胰岛素信号分子的磷酸化增加。MES(12V)+轻度HS对高脂饮食小鼠肝脏胰岛素受体β亚单位(IRβ)和AKT的磷酸化也有促进作用。在高脂饲养的小鼠和db/db小鼠中，MES+HS治疗10分钟，每周两次，持续12-15周，显著降低空腹血糖和胰岛素水平，并改善胰岛素敏感性。治疗组小鼠的内脏脂肪和皮下脂肪重量显著降低，脂肪肝明显改善，脂肪细胞体积缩小。我们的发现表明，MES和HS的结合缓解了糖尿病小鼠模型的胰岛素抵抗，改善了脂肪代谢，部分是通过增强胰岛素信号通路。
Low-intensity electrical current (or mild electrical stimulation; MES) influences signal transduction and activates phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance. In addition, it was also previously reported that heat shock protein 72 (Hsp72) alleviates hyperglycemia. Thus, we applied MES in combination with heat shock (HS) to in vitro and in vivo models of insulin resistance. Here we show that 10-min treatment with MES at 5 V (0.1 ms pulse duration) together with HS at 42°C increased the phosphorylation of insulin signaling molecules such as insulin receptor substrate (IRS) and Akt in HepG2 cells maintained in high-glucose medium. MES (12 V)+mild HS treatment of high fat-fed mice also increased the phosphorylation of insulin receptor β subunit (IRβ) and Akt in mice liver. In high fat-fed mice and db/db mice, MES+HS treatment for 10 min applied twice a week for 12–15 weeks significantly decreased fasting blood glucose and insulin levels and improved insulin sensitivity. The treated mice showed significantly lower weight of visceral and subcutaneous fat, a markedly improved fatty liver and decreased size of adipocytes. Our findings indicated that the combination of MES and HS alleviated insulin resistance and improved fat metabolism in diabetes mouse models, in part, by enhancing the insulin signaling pathway.
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影响因子：
7.7
作者：
Marchesini, G;Brizi, M;Melchionda, N
通讯作者：
Melchionda, N
影响因子：
7.4
作者：
Ainsworth, L;Budelier, K;Sluka, KA
通讯作者：
Sluka, KA
影响因子：
7.7
作者：
Cha, Dae Ryong;Zhang, Xiaoyan;Guan, Youfei
通讯作者：
Guan, Youfei
DOI：
10.1016/j.bbrc.2005.04.096
发表时间：
2005-06-17
影响因子：
3.1
作者：
Kobayashi, T;Goto, K;Yoshioka, T
通讯作者：
Yoshioka, T
影响因子：
7.7
作者：
Daitoku, H;Yamagata, K;Fukamizu, A
通讯作者：
Fukamizu, A