title: Insulin receptor activation through its accumulation in lipid rafts by mild electrical stress.
abstract: Insulin resistance is due to the reduced cellular response to insulin in peripheral tissues. The interaction of insulin with its receptor is the first step in insulin action and thus the identified target of insulin resistance. It has been well established that defects or mutations in the insulin receptor (IR) cause insulin resistance. Therefore, an IR activator might be a novel therapeutic approach for insulin resistance. Our previous report showed that mild electrical stress (MES) enhanced the insulin-induced signaling pathway. However, the molecular mechanism of the effect of MES remains unclear. We assessed the effect of MES, which is characterized by low-intensity direct current, on insulin signaling in vitro and in vivo. Here, we showed that MES activated the insulin signaling in an insulin-independent manner and improved insulin resistance in peripheral tissues of high fat-fed mice. Moreover, we found that MES increased the localization of IR in lipid rafts and enhanced the level of phosphorylated Akt in insulin-resistant hepatic cells. Ablation of lipid rafts disrupted the effect of MES on Akt activation. Our findings indicate that MES has potential as an activator of IR in an insulin-independent manner, and might be beneficial for insulin resistance in type 2 diabetes.
authors: Department of Molecular Medicine, Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, Kumamoto, Japan.
authors: Saori
authors: S
authors: Morino-Koga
authors: Shuichiro
authors: S
authors: Yano
authors: Tatsuya
authors: T
authors: Kondo
authors: Yuichiro
authors: Y
authors: Shimauchi
authors: Shingo
authors: S
authors: Matsuyama
authors: Yuka
authors: Y
authors: Okamoto
authors: Mary Ann
authors: MA
authors: Suico
authors: Tomoaki
authors: T
authors: Koga
authors: Takashi
authors: T
authors: Sato
authors: Tsuyoshi
authors: T
authors: Shuto
authors: Hidetoshi
authors: H
authors: Arima
authors: Ikuo
authors: I
authors: Wada
authors: Eiichi
authors: E
authors: Araki
authors: Hirofumi
authors: H
authors: Kai
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004558:Electric Stimulation; D056945:Hep G2 Cells; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013312:Stress, Physiological
chemical_list: D007328:Insulin; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt