2012 Fiscal Year Final Research Report
To elucidate the role of prpglucagon-derived peptides in glucose metabolism
| 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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| Keywords | インスリン分泌 / グルカゴン / glucose-dependent insulinotropic polypeptide (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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Research Products
(9 results)
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[Journal Article] Ectopic expression of GIP in pancreatic β-cells maintains enhanced insulin secretion in mice with complete absence of proglucagon-derived peptides2013
Author(s)
Fukami A, Seino Yus, Ozaki N, Yamamoto M, Sugiyama C, Sakamoto-Miura E, Himeno T, Takagishi Y, Tsunekawa S Ali S, Drucker DJ Murata Y, Seino Yut, Oiso Y, Hayashi Y (責任著者).
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Journal Title
Diabetes
Volume: 62
Pages: 510-518
Peer Reviewed
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