Molecular biology of pancreatic islet β cell proliferation and failure
| Project/Area Number |
20591051
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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 | The University of Tokyo |
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Principal Investigator |
OHSUGI Mitsuru The University of Tokyo, 医学部附属病院, 助教 (00420216)
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| Co-Investigator(Renkei-kenkyūsha) |
KADOWAKI Takashi 東京大学, 医学部附属病院, 教授 (30185889)
UEKI Kohjiro 東京大学, 医学部附属病院, 准教授 (00396714)
KUBOTA Naoto 東京大学, 医学部附属病院, 特任 (50396719)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 膵β細胞 / IRS / CREB / CaMK / 糖尿病 / 代償性肥大 / lRS-2 / カルモジュリン依存性キナーゼ |
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| Research Abstract |
(1) High glucose levels or glucose stimulation predominantly control pancreatic β cell IRS-2 levels. (2) A transcription factor CREB is critical for regulating β cell IRS-2 expression levels. Calmodulin dependent kinase 4 is stimulated by glucose, and the kinase appears to be the key component of complex regulation of CREB activation in pancreatic β cells. (3) In models of pancreatic β cell failure, such as db/db mice, critical molecules of glucose sensing, including glucokinase and glucose transporter 2, are downregulated, thus leading to a net decrease in glucose flux to β cells. With resultant reduction in IRS-2 levels, pancreatic β cell lose a key component of adaptive β cell proliferation and survival.
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Class IA Phosphatidylinositol 3-Kinase in Pancreatic β Cells Controls Insulin Secretion by Multiple Mechanisms.2010
Author(s)
Hashimoto S, Okamoto M, Awazawa M, Okazaki Y, Ohsugi M, Inabe K, Umehara T, Yoshida M, Kakei M, Kitamura T, Luo J, Kulkarni RN, Kahn CR, Kasai H, Cantley LC, Kadowaki T
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Journal Title
Cell Metab. 12(6)
Pages: 619-32
Related Report
Peer Reviewed
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[Journal Article] Y, Ueki K, Kadowaki T2010
Author(s)
Okazaki Y, Eto K, Yamashita T, Okamoto M, Ohsugi M, Noda M, Terauchi
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Journal Title
Decreased Insulin Secretion and Accumulation of Triglyceride in beta Cells Overexpressing a Dominant-Negative Form of AMP-Activated Protein Kinase Endocr J. 57(2)
Pages: 141-52
Related Report
Peer Reviewed
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[Journal Article] CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity.2009
Author(s)
Nishimura S, Manabe I, Naga, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R
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Journal Title
Nat. Med. 15(8)
Pages: 914-20
Related Report
Peer Reviewed
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[Journal Article] Reconsideration of Insulin Signals Induced by Improved Laboratory Animal Diets, Japanese and American Diets, in IRS-2 Deficient Mice.2009
Author(s)
Hashimoto H, Arai T, Hikishima K, Ohnishi Y, Eto T, Ito M, Hioki K, Suzuki R, Ohsugi M, Saito M, Ueyama Y, Okano H, Yamauchi T, Kubota N, Ueki K, Tobe K, Tamaoki N, Kadowaki T, Kosaka K
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Journal Title
Exp Clin Endocrinol Diabetes. 117(10)
Pages: 577-86
Related Report
Peer Reviewed
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[Journal Article] Rimonabant ameliorates insulin resistance via both adiponectin-dependent and adiponectin-independent pathways.2009
Author(s)
Watanabe T, Kubota N, Kubota T, Takamoto I, Iwabu M, Awazawa M, Katsuyama H, Hasegawa C, Tokuyama K, Moroi M, Sugi K, Yamauchi T, Noda T, Nagai R, Terauchi Y, Tobe K, Ueki K, Kadowaki T
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Journal Title
J Biol Chem. 284(3)
Pages: 1803-12
Related Report
Peer Reviewed
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[Journal Article] An Efficient Reproductive Method for Irs2(-/-) Mice with C57BL/6JJcl Genetic Background.2008
Author(s)
Hashimoto H, Eto T, Kamisako T, Hoya N, Hatakeyama T, Arai T, Yokosuka M, Ohnishi Y, Ito M, Hioki K, Suzuki R, Ohsugi M, Saito M, Ueyama Y, Yamauchi T, Kubota N, Tobe K, Kadowaki T, Tamaoki N, Nomura T, Kosaka K
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Journal Title
Exp Anim. 57
Pages: 407-11
NAID
Related Report
Peer Reviewed
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[Journal Article] Fulminant type 1 diabetes mellitus observed in insulin receptor substrate 2 deficient mice.2008
Author(s)
Arai T, Hashimoto H, Kawai K, Mori A, Ohnishi Y, Hioki K, Ito M, Saito M, Ueyama Y, Ohsugi M, Suzuki R, Kubota N, Yamauchi T, Tobe K, Kadowaki T, Kosaka K
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Journal Title
Clin Exp Med. 8
Pages: 93-9
Related Report
Peer Reviewed
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[Journal Article] Dynamic functional relay between insulin receptor substrate 1 and 2 in hepatic insulin signaling during fasting and feeding.2008
Author(s)
Kubota N, Kubota T, Itoh S, Kumagai H, Kozono H, Takamoto I, Mineyama T, Ogata H, Tokuyama K, Ohsugi M, Sasako T, Moroi M, Sugi K, Kakuta S, Iwakura Y, Noda T, Ohnishi S, Nagai R, Tobe K, Terauchi Y, Ueki K, Kadowaki T
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Journal Title
Cell Metab. 8(1)
Pages: 49-64
Related Report
Peer Reviewed
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