| Project/Area Number |
17590269
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
OBATA Toshiyuki The University of Tokushima, Institute for Enzyme Research, Associate Professor, 分子酵素学研究センター, 助教授 (40325296)
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| Co-Investigator(Kenkyū-buntansha) |
EBINA Yousuke The University of Tokushima, Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (00112227)
YUASA Tomoyuki The University of Tokushima, Institute for Enzyme Research, Research Associate, 分子酵素学研究センター, 助手 (50304556)
YOKOYAMA Kazuhiro The University of Tokushima, Institute for Enzyme Research, COE Researcher, 分子酵素学研究センター, COE研究員 (00346602)
TESHIGAWARA Kiyoshi The University of Tokushima, Institute for Enzyme Research, COE Researcher, 分子酵素学研究センター, COE研究員 (40403737)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Soluble Insulin Receptor / diabetes / glycemic marker / シグナル伝達 / 血中可溶性インスリン受容体 / 生理活性 / インスリン受容体 |
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| Research Abstract |
Insulin binds to the a-subunit of the insulin receptor (IRα), and subsequently exerts its effects in the cells. The soluble ectodomains of several receptors were found to circulate in the plasma. Therefore, we hypothesized that soluble human IR ectodomain (α-subunit and a part of β-subunit) may exist in the plasma of diabetes patients.
We identified soluble hIR ectodomain in human plasma by a two-step purification followed by immunoblotting and by a gel-filtration chromatography. Furthermore, we established a hIRa-specific enzyme-linked immunosorbent assay (ELISA) and measured the plasma IRa levels in patients with diabetes mellitus (DM). We also investigated this phenomenon in streptozotocin-induced diabetic hIR transgenic mice.
The soluble hIRa, but not intact hIRβ or whole hIR, exists in human plasma. The plasma IRa levels were significantly higher in patients with type 2 and type 1 DM than in control subjects (2.26 ± 0.80 (type 2, n=473) and 2.00 ± 0.60 ng/ml (type 1, n=53) vs. 1.59 ± 0.40 ng/ml (control, n=123), p<0.001 vs. the control). The plasma IRa level was positively correlated with the blood glucose level and 10-20% of the insulin in patient plasma bound to hIRa. In the in vivo experiments using diabetic hIR transgenic mice, hyperglycemia was confirmed to increase the plasma hIRa level and the half-life was estimated to be6 〜6h.
We propose that the increased hIRa level appeared to be more rapid glycemic marker compared to HbA1c or glycoalbumin.
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