1999 Fiscal Year Final Research Report Summary
treatment using adenovirus vector
| Project/Area Number |
09357009
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Yamaguchi University |
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Principal Investigator |
OKA Yoshitomo Yamaguchi University School of Medicine, Professor, 医学部, 教授 (70175256)
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| Co-Investigator(Kenkyū-buntansha) |
KATAGIRI Hideki Tokyo University Hospital, Clinical Fellow, 医学部・附属病院, 医員(臨床)
INOUE Hiroshi Yamaguchi University Hospital, Assistant Professor, 医学部・附属病院, 助手 (20294639)
TANIZAWA Yukiko Yamaguchi University School of Medicine, Professor, 医学部・附属病院, 講師 (00217142)
EMOTO Masahiro Yamaguchi University Hospital, Research Associate, 医学部・附属病院, 助手 (50294640)
INUKAI Kouichi Tokyo University Hospital, Clinical Fellow, 医学部・附属病院, 医員(臨床)
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| Project Period (FY) |
1997 – 1999
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| Keywords | diabetes mellitus / adenovirus vector / insulin / glucose transport / PI3-kinase / sulfonylurea receptor / Wolfram syndrome / persistent hyperinsulinemic hypoglycemia of infancy |
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| Research Abstract |
We have studied insulin signaling toward stimulation of glucose transport in 3T3-L1 adipocytes using recombinant adenovirus. Expression of dominant negative p85 submit of PI3-kinase inhibited insulin-stimulated glucose transeport activity and GLUT4 translocation, indicating an important role of PI3-kinase activation in insulin-stimulated glucose transport. However, a discrepancy was observed between PI3-kinase activity and glucose transport activity, suggesting a possibility that a different pathway(s) is involved in insulin-stimulated intrinsic activity of glucose transport. In contrast to the involvement of PI3-kinase, ras activation is not involeved in insulin-stimulated glucose transeport, since overexpression of dominant negative Ras did not affect insulin-stimulated glucose transport.
We have also studied insulin secretion mechanism using recombinant adenovirus. Mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (mGPDH) was decreased in pancreatic islets of GK rats which show defects in insulin serection. Since defects in insulin secretion had been ascribed to decreased mGPDH activity, we corrected the decreased mGPDH activity by overexpressing mGPDH using adenovirus vector. However, defects in insulin secretion was not corrected, indicating decreased mGPDH activity is not responsible for insulin secretion defects in GK rats. Employing positional cloning method, we have cloned a novel gene responsible for Wolfram syndrome characterized by non-immune insulin dependent diabetes mellitus and optic atrophy. This gene, designated WFS1, must have an important role in survival of pancreatic beta cells and neuronal cells. We also found mutations in sulfonylurea receptor gene in three Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy and elucidated the molecular mechanism for defests in insulin secretion, especially a possible binding site of ADP and ATP for sulfonylurea receptor.
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