研究発表を行った学会； 66th scientific sessions (American Diabetes Association)
　　　２００６年６月　９日〜１３日 ( Washington, D.C. )
タイトル； Mild Electrical Stimulation with Hyperthermia Ameliorates Insulin Resistance and Glucose Homeostasis in Mice Models of Type 2 Diabetes
発表者；森野　沙緒里　氏
　　　（熊本大学　大学院医学薬学研究部　遺伝子機能応用学分野）
Abstract；
Heat shock protein 72 (Hsp72) is the major inducible heat shock protein, which plays a significant role in protein synthesis, folding and translocation into organelles. It has been reported that down-regulation of Hsp72 mRNA in skeletal muscle from patients with type 2 diabetes may be associated with insulin resistance. We hypothesized that induction of Hsp72 in skeletal muscle may ameliorate insulin resistance in type 2 diabetic patients. Therefore, we developed a new device, which can effectively induce the expression of Hsp72 by combination of mild electrical stimulation and hyperthermia (0.175 V, 42｡｡C, 10 min). Here we show that this combined treatment synergistically increased the expression of Hsp72 in the skeletal muscle of the mice model of type 2 diabetes (high-fat-fed and db/db mice). In high-fat-fed mice, the treatment significantly decreased fasting blood glucose levels by 20% and fasting serum insulin levels by 38%. In addition, serum adiponectin and UCP1 mRNA expression in brown adipose tissue of treated mice were also increased by 94% and 45%, respectively. Glucose tolerance upon i.p.GTT was also improved at 15, 30, 60 min timepoints. Moreover, increased insulin-stimulated GLUT4 translocation was observed in skeletal muscle of the treated mice. Surprisingly, the treated mice showed significantly lower weight of visceral fat and subcutaneous fat (34% and 44% decrease v.s. untreated controls, respectively), although there was no difference in food intake between the two groups. Histological examinations showed that fatty liver was markedly improved and the size of adipocytes was also decreased in treated mice. These ameliorations in glucose metabolism and fat accumulation were also observed in db/db mice. Our findings indicate that the combined treatment of mild electrical stimulation and hyperthermia, which can induce Hsp72, is a novel potential therapeutic approach for the metabolic abnormalities in patients with type 2 diabetes and/or metabolic syndrome.