| Project/Area Number |
22590974
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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 | Nagoya University |
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Principal Investigator |
OZAKI Nobuaki 名古屋大学, 総合保健体育科学センター, 特任准教授 (70378082)
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| Co-Investigator(Kenkyū-buntansha) |
OISO Yutaka 名古屋大学, 医学系研究科, 教授 (40203707)
HAYASHI Yoshitaka 名古屋大学, 環境医学研究所, 准教授 (80420363)
SEINO Yusuke 名古屋大学, 医学系研究科, 寄附講座助教 (80534833)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | インスリン分泌 / グルカゴン / glucose-dependent insulinotropic polypeptide (GIP) / GIP |
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| Research Abstract |
Glucagon and glucagon-like peptide-1 (GLP-1) are produced in pancreatic α-cells and enteroendocrine L-cells, respectively, in a tissue-specific manner from the same precursor, proglucagon, that is encoded by glucagon gene (Gcg), and play critical roles in glucose homeostasis. Here we studied glucose homeostasis andβ-cell function of Gcg-deficient mice that are homozygous for a Gcg-GFP knock-in allele (Gcg^gfp/gfp). Gcg^gfp/gfpmice displayed improved glucose tolerance and enhanced insulin secretion, as assessed by both oral and intraperitoneal glucose tolerance tests. Responses of glucose-dependent insulinotropic polypeptide (GIP) to both oral and intraperitoneal glucose loads were unexpectedly enhanced in Gcg^gfp/gfpmice and immunohistochemistry localized GIP to pancreatic β-cells of Gcg^gfp/gfpmice. Furthermore secretion of GIP in response to glucose was detected in isolated islets of Gcg^gfp/gfpmice. Blockade of GIP action in vitro and in vivo by cAMP antagonism and genetic deletion of the GIP receptor, respectively, almost completely abrogated enhanced insulin secretion in Gcg^gfp/gfpmice. These results indicate that ectopic GIP expression in β-cells maintains insulin secretion in the absence of proglucagon-derived peptides, revealing a novel compensatory mechanism for sustaining incretin hormone action in islets.
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