| Co-Investigator(Kenkyū-buntansha) |
ISHIHARA Hisamitsu Faculty of Medicine, The University of Tokyo, Postdoctoral fellow, 医学部・附属病院, 医員
KATAGIRI Hideki Faculty of Medicine, The University of Tokyo, Postdoctoral fellow, 医学部・附属病院, 医員
TSUKUDA Katsunori Faculty of Medicine, The University of Tokyo, Postdoctoral fellow, 医学部・附属病院, 医員
OGIHARA Takehide Faculty of Medicine, The University of Tokyo, Postdoctoral fellow, 医学部・附属病院, 医員
FUNAKI Makoto Faculty of Medicine, The University of Tokyo, Postdoctoral fellow, 医学部・附属病院, 医員
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| Research Abstract |
Activation of p85/p110 type PI-kinase has been shown to be necessary for the insulin-induced glucose metabolism. Thus, we have investigated (1) The altered p85/p110 type PI-kinase activation in the insulin resistant condition, and (2) The alteration of the cellular content of phosphorylated phospholipid by p85/p110 type PI-kinase end its role on cellular activities.
(1) The altered p85/p110 type PI-kinase activation in the insulin resistant condition obesity and high-fat diet are regarded as the most common causes of insulin resistance in Japanese population. We reported that obesity induced by overeating leads to the marked impairment of p85/p110 type PI-kinase activation in either liver, muscle or fat tissues. In contrast, high-fat diet feeding resulted in moderate impairment of p85/p110 type PI-kinase activation in muscle and fat tissues, however, interestingly, in the liver the activation was markedly enhanced. These results indicate that the mechanism of insulin resistance caused by high-fat diet is quite different from that by overeating.
(2) The alteration of the cellular content of phosphorylated phospholipid by p85/p110 type PI-kinase. We observed activation of p85/p110 type PI-kinase resulted in the increased cellular content of not only PI3-P, PI3, 4-P2, PI3, 4, 5-P3 but also PI4-P and PI4, 5-P2 markedly. This suggests that p85/p110 type PI-kinase possesses a high PI 4-kinase activity. In addition, we observed the PI 4-kinase activity of p85/p110 type PI-kinase is involved in the actin rearrangement and the translocation of glucose transporter to the cell surface. These findings are surprising and can be a breakthrough to understand the molecular mechanism of insulin action and/or insulin resistance in NIDDM patients.
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