Mechanism of insulin-induced GLUT4 down-regulation through retromer inhibition
| Project/Area Number |
23591295
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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 |
Metabolomics
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| Research Institution | Gunma University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | インスリン / 活性酸素 / レトロマー / 脂肪細胞 / NADPHオキシダーゼ / GLUT4 / GLUUT4 / レトロマー複合体 / タンパク分解 |
|---|
| Research Abstract |
Long term insulin stimulation causes GLUT4 depletion. This effect is caused mainly by accelerated lysosomal degradation of GLUT4. We show that insulin acutely dissociated retromer from the LDM membranes of 3T3-L1 adipocytes that was accompanied by disruption of the interaction of Vps35 with sortilin. This insulin effect was dependent on protein kinase CK2 but not PI3-kinase or Erk 1/2. Knockdown of Vps26 decreased GLUT4 to a level comparable with that with insulin stimulation for 4 h. Vps35 with a mutation in the CK2 phosphorylation motif was resistant to insulin-induced dissociation from the low density microsomal membrane, and its overexpression attenuated GLUT4 down-regulation with insulin. Insulin-generated hydrogen peroxide was an upstream mediator of the insulin action on retromer and GLUT4. These results suggested that insulin-generated oxidative stress switches the GLUT4 sorting direction to lysosomes through inhibition of the retromer function in a CK2-dependent manner.
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] A Novel Regulatory Function of Sweet Taste-Sensing Receptor in Adipogenic Differentiation of 3T3-L1 Cells2013
Author(s)
Masubuchi, Y., Nakagawa, Y., Ma, J., Sasaki, T., Kitamura, T., Yamamoto, Y., Kurose, H., Kojima, I., Shibata, H.
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Journal Title
PLoS ONE
Volume: 8
Issue: 1
Pages: e54500-e54500
DOI
Related Report
Peer Reviewed
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[Journal Article] Miglitol prevents diet-induced obesity by stimulating brown adipose tissue and energy expenditure independent of preventing the digestion of carbohydrates2013
Author(s)
Sasaki T, Shimpuku M, Kitazumi T, Hiraga H, Nakagawa Y, Shibata H, Okamatsu-Ogura Y, Kikuchi O, Kim HJ, Fujita Y, Maruyama J, Susanti VY, Yokota-Hashimoto H, Kobayashi M, Saito M, Kitamura T
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Journal Title
Endocr J
Volume: Vol.60
Pages: 1117-1129
NAID
URL
Related Report
Peer Reviewed
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