| 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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| 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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