2005 Fiscal Year Final Research Report Summary
BIOLOGICAL ROLES OF NEW TRANSCRIPTION FACTOR FOR GLUCOSE METABOLISM(ChREBP) IN PANCREATIC ISLET CELLS
| Project/Area Number |
15590963
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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 |
Metabolomics
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| Research Institution | KURUME UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
KAWAGUCHI Takumi Kurume University School of Medicine, Department of Digestive Disease Information & Research, Assistant, 医学部, 助手 (00320177)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Masaru Kurume University School of Medicine, Department of Medicine, Assistant Professor, 医学部, 講師 (00241175)
KOGA Hironori Kurume University School of Medicine, Department of Medicine, Assistant Professor, 医学部, 講師 (90268855)
TANIGUCHI Eitaro Kurume University School of Medicine, Department of Medicine, Assistant, 医学部, 助手 (50341318)
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| Project Period (FY) |
2003 – 2005
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| Keywords | ChREBP / INS-1 cell / insulin secretion / gene mutation / insulin receptor / diabetes mellitus / HepG2 cell / insulin receptor substrate |
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| Research Abstract |
Diabetes mellitus is characterized by the impairment of glucose metabolism, however, the responsible molecules for the development of diabetes mellitus remains unclear. Recently, we have identified and characterize a transcription factor for glucose metabolism, carbohydrate responsive element binding protein(ChREBP). ChREBP activates the transcripton of liver-type pyruvate kinase gene. The aim of this study is to investigate the biological roles of ChREBP in pancreatic beta cell and hepatocytes, target cells of insulin.
The role of ChREBP in insulin secretion was investigated by using INS-1 cells. By transfection of ChREBP gene into INS-1 cell, ChREBP was overexpressed in INS-1 cell and insulin levels in culture media was altered. We also examined the mutation of ChERBP gene in patients with diabetes mellitus. Although regulation sites of ChREBP were investigated, any mutation of gene was not identified. In addition, we investigated the mechanisms for hepatic insulin resistance. Although there was no significant change in insulin receptor, down-regulation of hepatic insulin receptor substrate 1/2, central molecules for intracellular insulin signaling cascade, was seen in HepG2 cells showing increased insulin resistance.
In this study, we demonstrated the biological roles of ChREBP in INS-1 cells and the involvement of hepatocyte, a target cell of insulin, in the development of insulin resistance. Thus, ChREBP and insulin receptor substrate 1/2 may be responsible molecules for the development of diabetes mellitus.
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