Novel regulatory mechanism of insulin activity through IRS monoubiquitination
Project/Area Number |
24790928
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Metabolomics
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Research Institution | Hiroshima University |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | インスリン / インスリン様成長因子 / インスリン受容体基質 / 糖尿病 / ユビキチン / 細胞内シグナル / Nedd4 / Epsin1 / 細胞内シグナル伝達 / 国際情報交換 スウェーデン |
Outline of Final Research Achievements |
Insulin is a hormone that regulates blood glucose levels. Insulin-like growth factor (IGF) is another hormone similar in molecular structure to insulin, and IGF promotes cell proliferation and body growth. We previously found that insulin receptor substrate (IRS), a protein that mediates insulin/IGF intracellular signaling, is functionally changed by its modification called as "monoubiquitination", and it leads to the enhancement of insulin/IGF signaling and induction of their bioactivities. In this study, we elucidated the detailed molecular mechanisms underlying the enhancement of insulin/IGF signaling by IRS monoubiquitination. Furthermore, we found that, when the amounts of nutrition given to hepatocytes are changed, hepatic insulin sensitivity also changed through this novel mechanism. This finding is thought to be important for understanding pathogenic mechanism of diabetes.
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasma glucagon-like peptide-1 level in a rodent model.2015
Author(s)
Hirofumi Okubo, Yusuke Nakatsu, Hideyuki Sakoda, Akifumi Kushiyama, Midori Fujishiro, Toshiaki Fukushima, Yasuka Matsunaga, Haruya Ohno, Masayasu Yoneda, Hideaki Kamata, Takanori Shinjo, Misaki Iwashita, Fusanori Nishimura, and Tomoichiro Asano
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Journal Title
Am. J. Physiol. Gastrointest. Liver Physiol.
Volume: 308
Issue: 2
Pages: 151-158
DOI
Related Report
Peer Reviewed
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[Journal Article] Nedd4-induced mono-ubiquitination of IRS-2 enhances IGF signaling and mitogenic activity.2015
Author(s)
Toshiaki Fukushima, Hidehito Yoshihara, Haruka Furuta, Fumihiko Hakuno, Jing Luan, Cunming Duan, Yasushi Saeki, Keiji Tanaka, Shun-Ichiro Iemura, TohruNatsume, Kazuhiro Chida, Yusuke Nakatsu, Hideaki Kamata, Tomoichiro Asano, and Shin-Ichiro Takahashi
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Journal Title
Nature communications
Volume: 6
Issue: 1
Pages: 6780-6780
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Familial short stature is associated with a novel dominant-negative heterozygous insulin-like growth factor 1 receptor (IGF1R) mutation2014
Author(s)
Kawashima Y, Hakuno F, Okada SI, Hotsubo T, Kinoshita T, Fujimoto M, Nishimura R, Fukushima T, Hanaki K, Takahashi SI, Kanzaki S
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Journal Title
Clinical Endocrinology (Oxf)
Volume: Epub ahead of print
Issue: 2
Pages: 1-3
DOI
Related Report
Peer Reviewed
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[Journal Article] Lactobacillus casei strain Shirota protects against non-alcoholic steatohepatitis development in a rodent model2013
Author(s)
Okubo H, Sakoda H, Kushiyama A, Fujishiro M, Nakatsu Y, Fukushima T, Matsunaga Y, Kamata H, Asahara T, Yoshida Y, Chonan O, Iwashita M, Nishimura F, Asano T
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Journal Title
American Journal Physiolgy-Gastrointestinal and Liver Physiogy
Volume: 305
Issue: 12
Pages: 911-918
DOI
Related Report
Peer Reviewed
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[Journal Article] Par14 associates with IRS-1, thereby enhancing insulin-induced IRS-1 phosphorylation and metabolic actions.2013
Author(s)
Zhang J, Nakatsu Y, Sinjo T, Guo Y, Sakoda H, Yamamotoya T, Otani Y, Okubo H, Kushiyama A, Fujishiro M, Fukushima T, Tsuchiya Y, Kamata H, Nishimura F, Katagiri H, Takahashi SI, Kurihara H, Uchida T, Asano T.
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Journal Title
Journal of Biological Chemistry
Volume: 288
Issue: 28
Pages: 20692-20701
DOI
Related Report
Peer Reviewed
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[Journal Article] Resistin-Like Molecule β Is Abundantly Expressed in Foam Cells and Is Involved in Atherosclerosis Development.2013
Author(s)
Kushiyama A, Sakoda H, Oue N, Okubo M, Nakatsu Y, Ono H, Fukushima T, Kamata H, Nishimura F, Kikuchi T, Fujishiro M, Nishiyama K, Aburatani H, Kushiyama S, Iizuka M, Taki N, Encinas J, Sentani K, Ogonuki N, Ogura A, Kawazu S, Yasui W, Higashi Y, Kurihara H, Katagiri H, Asano T.
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Journal Title
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 33
Issue: 8
Pages: 1986-1993
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Integrator complex plays anessential role inadipose differentiation2013
Author(s)
Otani Y, Nakatsu Y, Sakoda H, Fukushima T, Fujishiro M, Kushiyama A, Okubo H, Tsuchiya Y, Ohno H, Takahashi S, Nishimura F, Kamata H, Katagiri H, Asano T.
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 434
Issue: 2
Pages: 197-202
DOI
Related Report
Peer Reviewed
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[Journal Article] Valsartan, independently of AT1 receptor or PPARγ, suppresses LPS-induced macrophage activation and improves insulin resistance in cocultured adipocytes.2012
Author(s)
Iwashita M, Sakoda H, Kushiyama A, Fujishiro M, Ohno H, Nakatsu Y, Fukushima T, Kumamoto S, Tsuchiya Y, Kikuchi T, Kurihara H, Akazawa H, Komuro I, Kamata H, Nishimura F, Asano T.
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Journal Title
American Journal of Physiology - Endocrinology and Metabolism
Volume: 302
Issue: 3
Pages: 286-296
DOI
Related Report
Peer Reviewed
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[Journal Article] Xanthine Oxidoreductase Is Involved in Macrophage Foam Cell Formation and atherosclerosis development2012
Author(s)
Kushiyama A, Okubo H, Sakoda H, Kikuchi T, Fujishiro M, Sato H, Kushiyama S, Iwashita M, Nishimura F, Fukushima T, Nakatsu Y, Kamata H, Kawazu S, Higashi Y, Kurihara H, Asano T.
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 32
Issue: 2
Pages: 291-298
DOI
Related Report
Peer Reviewed
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[Journal Article] Phosphatidylinositol 3-kinase binding protein, PITKAP/XB130 is required for cAMP-induced amplification of IGF mitogenic activity in FRTL-5 thyroid cells.2012
Author(s)
Yamanaka D, Akama T, Fukushima T, Nedachi T, Kawasaki C, Chida K, Minami S, Suzuki K, Hakuno F, Takahashi S-I.
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Journal Title
Mol Endocrinol
Volume: 26
Issue: 6
Pages: 1043-1055
DOI
Related Report
Peer Reviewed
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[Journal Article] Insulin/insulin-like growth factor (IGF) stimulation abrogates an association between a deubiquitinating enzyme USP7 and insulin receptor substrates (IRSs) followed by proteasomal degradation of IRSs2012
Author(s)
Yoshihara H, Fukushima T, Hakuno F, Saeki Y, Tanaka K, Ito A, Yoshida M, Iemura S, Natsume T, Asano T, Chida K, Girnita L, Takahashi S-I
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 423
Issue: 1
Pages: 122-127
DOI
Related Report
Peer Reviewed
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[Journal Article] Phosphatidylinsitol 3-kinase (PI3K) activity bound to insulin-like growth factor-I (IGF-I) receptor, which is continuously sustained by IGF-I stimulation, is required for IGF-I-induced cell proliferation.2012
Author(s)
Fukushima T, Nakamura Y, Yamanaka D, Shibano T, Chida K, Minami S, Asano T, Hakuno F, Takahashi S-I.
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Journal Title
J. Biol. Chem.
Volume: 287
Issue: 35
Pages: 29713-29721
DOI
Related Report
Peer Reviewed
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[Journal Article] Role of Pin1 in the pathogenesis of non-alcoholic steatohepatitis in a rodent model2012
Author(s)
Nakatsu Y, Otani Y, Sakoda H, Zhang J, Guo Y, Okubo H, Kushiyama A, Fujishiro M, Kikuchi T, Fukushima T, Ohno H, Tsuchiya Y, Kamata H, Nagamachi A, Inaba T, Nishimura F, Katagiri H, Takahashi SI, Kurihara H, Uchida T, Asano T
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Journal Title
J Biol Chem
Volume: 287
Issue: 53
Pages: 44526-44535
DOI
Related Report
Peer Reviewed
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[Presentation] The deubiquitinating enzyme, USP9X positively regulates IGF-I-dependent cell growth by inhibition of degradation of insulin receptor substrate (IRS)-2 in cancer cells2015
Author(s)
Haruka Furuta, Hidehito Yoshihara, Toshiaki Fukushima, Yasushi Saeki, Keiji Tanaka, Akihiro Ito, Minoru Yoshida, Tomoichio Asano, Kazuhiro Chida, Fumihiko Hakuno, Shin-Ichiro Takahashi
Organizer
Gordon Research Conference: IGF and Insulin System in Physiology and disease
Place of Presentation
Ventura, USA
Year and Date
2015-03-08 – 2015-03-13
Related Report
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[Presentation] The deubiquitinating enzyme, USP9X positively regulates insulin-like growth factor (IGF)-dependent cell growth by inhibition of degradation of IGF-I receptor (IGF-IR) and insulin receptor substrate (IRS)-2 in cancer cells2014
Author(s)
Haruka Furuta, Hidehito Yoshihara, Toshiaki Fukushima, Yasushi Saeki, Akihiro Ito, Claire Worrall, Leonard Girnita, Keiji Tanaka, Minoru Yoshida, Tomoichio Asano, Kazuhiro Chida, Fumihiko Hakuno, Shin-Ichiro Takahashi
Organizer
The International Congress of the GRS and the IGF Society
Place of Presentation
Singapore
Year and Date
2014-10-15 – 2014-10-18
Related Report
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[Presentation] インスリン受容体RNAの選択的スプライシングの新しい制御機構2014
Author(s)
Yuka Narita, Atsufumi Ozoe, Toshiaki Fukushima, Naoyuki Kataoka, Akihiro Ito, Minoru Yoshida, Tomoichiro Asano, Kazuhiro Chida, Fumihiko Hakuno, Shin-Ichiro Takahashi
Organizer
Japan Endocrine Society's Annual Meeting
Place of Presentation
福岡
Related Report
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[Presentation] Nedd4-IRS2 complex: mechanisms of the complex formation and its roles in prostate cancer cell proliferation2013
Author(s)
Toshiaki Fukushima, Hidehito Yoshihara, Haruka Furuta, Fumihiko Hakuno, Kazuhiro Chida, Yasushi Saeki, Keiji Tanaka, Akihiro Ito, Minoru Yoshida, Yusuke Nakatsu, Hideaki Kamata, Shin-Ichiro Takahashi, Tomoichio Asano
Organizer
Annual Meeting of the Molecular Biology Society of Japan
Place of Presentation
神戸
Related Report
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[Presentation] The deubiquitinating enzyme, USP9X positively regulates insulin-like growth factor (IGF)-dependent cell growth by inhibition of degradation of IGF-I receptor (IGF-IR) and insulin receptor substrate (IRS)-2 in cancer cells2013
Author(s)
Haruka Furuta, Hidehito Yoshihara, Toshiaki Fukushima, Yasushi Saeki, Keiji Tanaka, Akihiro Ito, Minoru Yoshida, Tomoichio Asano, Kazuhiro Chida, Fumihiko Hakuno, Shin-Ichiro Takahashi
Organizer
Annual Meeting of the Molecular Biology Society of Japan
Place of Presentation
神戸
Related Report
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[Presentation] PGAM5, a mitochondrial protein phosphatase, regulates the serine/threonine phosphorylation status and stability of insulin receptor substrates.2013
Author(s)
Yosuke Yoneyama, Junichi Inobe, Yukako Kida, Toshiaki Fukushima, Shiori Sekine, Tomoichiro Asano, Kazuhiro Chida, Kohsuke Takeda, Fumihiko Hakuno, Shin-Ichiro Takahashi
Organizer
Annual Meeting of the Molecular Biology Society of Japan,
Place of Presentation
神戸
Related Report
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[Presentation] Nedd4 potentiates IRS-2-mediated insulin/IGF signals and bioactivities.2012
Author(s)
Fukushima T, Yoshihara H, Hakuno F, Saeki Y, Tanaka K, Ito A, Yoshida M, Nakatsu Y, Sakoda H, Kamata H, Takahashi SI, Asano T
Organizer
Annual Meeting of the Japan Diabetes Society
Place of Presentation
横浜
Related Report
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[Presentation] Ubiquitin ligase Nedd4 interacts with insulin receptor substrate (IRS)-2 in response to humoral/nutritional stimuli, thereby enhancing IRS-2-mediated IGF/insulin signals through a novel mechanism.2012
Author(s)
Fukushima T, Yoshihara H, Hakuno F, Saeki Y, Tanaka K, Ito A, Yoshida M, Chida K, Sakoda H, Asano T, Takahashi SI.
Organizer
The 6th International Congress of the GRS and the IGF Society
Place of Presentation
ドイツ ミュンヘン
Related Report
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