Analysis of molecular mechanisms underlying induction of insulin resistance in skeletal muscle
| Project/Area Number |
25460365
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
IJUIN TAKESHI 神戸大学, 医学(系)研究科(研究院), 助教 (00361626)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | SKIP / 骨格筋 / インスリンシグナル / インスリン抵抗性 / 小胞体ストレス / GRP78 / ２型糖尿病 / 筋小胞体 / ＰＩＰ３ / 糖尿病 / インスリン / 小胞体 |
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| Outline of Final Research Achievements |
Insulin resistance is characterized as a pathogenic factor in Type 2 diabetes. Here we show that skeletal muscle and kidney-enriched inositol polyphosphate phosphatase (SKIP), a phosphatidylinositol-3,4,5-trisphosphate (PIP3) phosphatase, and glucose-regulated protein 78 (GRP78) are implicated in inhibition of insulin-dependent PI 3-kinase signaling in skeletal muscle. We also show that SKIP links ER stress to insulin resistance in skeletal muscle. SKIP expression was increased due to ER stress, and was higher in the skeletal muscle isolated from high fat diet-fed mice and db/db mice than that from wild-type mice. Mechanistically, ER stress promotes activating transcription factor 6 (ATF6) and X-box binding protein 1 (XBP1)-dependent expression of SKIP. These findings underscore the specific and prominent role of SKIP in the development of insulin resistance in skeletal muscle.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Phosphatidylinositol 4-phosphate in the Golgi apparatus regulates cell-cell adhesion and invasive cell migration in human breast cancer.2014
Author(s)
Tokuda, E., Itoh, T., Hasegawa, J., Ijuin, T., Takeuchi, Y., Irino, Y., Fukumoto, M., Takenawa, T.
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Journal Title
Cancer Res.
Volume: 74
Issue: 11
Pages: 3054-3066
DOI
Related Report
Peer Reviewed / Open Access
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