title: Mild electrical stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling.
abstract: 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 degrees 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 beta subunit (IRbeta) 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.
authors.affiliation: Department of Molecular Medicine, Faculty of Medical and Pharmaceutical Sciences, Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, Kumamoto, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Morino
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kondo
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sasaki
authors.forename: Hironori
authors.initials: H
authors.lastname: Adachi
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Suico
authors.forename: Erika
authors.initials: E
authors.lastname: Sekimoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Matsuda
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shuto
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kai
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004558:Electric Stimulation; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D050884:HSP72 Heat-Shock Proteins; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt