| Project/Area Number |
24790944
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Endocrinology
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 日本人2型糖尿病 / GCN2 / アミノ酸 / 膵β細胞量 / mTORC1活性 / mTORC1 |
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| Research Abstract |
GCN2-/-mice fed a normal-chow diet (NCD) didn't exhibit any changes in glucose tolerance or pancreatic beta-cell mass. GCN2-/-mice fed a high-fat diet (HFD) exhibited significant aggravation in glucose tolerance and reduction in pancreatic beta-cell mass. Islets isolated from GCN2-/-mice showed significant increase in mTORC1 activity and decrease in insulin signaling. Next, we found that GCN2 was markedly activated in islets from mice fed a HFD. We also measured the concentration of amino acids, and found that it is reduced in islets from mice fed a HFD.
Our results showed that chronic activation of mTORC1 signal is one of the causes of reduction in pancreatic beta-cell mass in GCN2-/-mice. In islets from mice fed a HFD, the activation of GCN2, caused by the enhancement of translation of insulin, might contribute to maintenance of pancreatic beta-cell mass. We expect that GCN2-/-mice could be the models of the pathogenesis of T2DM in patients who have a SNP in GCN2.
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