Role of myokines and AMPK in skeletal muscle in streptozotocin-induced diabetec mice
| Project/Area Number |
17H04203
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | National Institute for Physiological Sciences |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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| Keywords | AMPK / ストレプトゾトシン糖尿病 / 骨格筋 / マイオカイン / myokine / ストレプトゾトシン / アディポカイン / adipokine / 糖尿病 |
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| Outline of Final Research Achievements |
AMP kinase (AMPK), a metabolic sensor that is activated by energy deficiency, plays an important role in the control of energy metabolism. We found that mice expressing dominant negative AMPK (DN-AMPK Tg) in skeletal muscle dramatically imporve metabolic abonormalities such as hyperglycemia, hyperlipidemia and high fatty acids levels of streptozotocin-treated diabeteci miceand extended the survival rate. Studies with recombinat proteins and neutral antibodies for myokines including IL-6 and myonectin revealed that the effects of DN-AMPK Tg in skeletal muscle on STZ diabetes are associated with changes in plasma myokine levles secreted from skeletal muscle.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、STZ糖尿病の代謝異常の一部が、インスリン欠乏だけでなく、骨格筋を始めとする臓器間相互ネットワーク異常に起因するとの考えに立ち、骨格筋選択的にAMPK活性を抑制したマウスにおいてSTZ糖尿病の代謝異常が改善するメカニズムを調べた。その結果、骨格筋選択的にAMPK活性を抑制した時の代謝改善効果が、骨格筋から分泌されるマイオカインによることを見出した。本研究結果は、骨格筋から分泌されるマイオカインが1型糖尿病の病態形成にも関与する可能性を示している。
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Report
(4 results)
Research Products
(58 results)
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[Journal Article] Hyperglycemia induces skeletal muscle atrophy via a WWP1-KLF15 axis.2019
Author(s)
Hirata Y, Nomura K, Senga Y, Okada Y, Kobayashi K, Okamoto S, Minokoshi Y, Imamura M, Takeda S, Hosooka T, Ogawa W.
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Journal Title
JCI Insight
Volume: 4
Pages: 124952-124952
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hypothalamic Neuronal Circuits Regulating Hunger-Induced Taste Modification2019
Author(s)
Fu O, Iwai Y, Narukawa M, Ishikawa AW, Ishii KK, Murata K, Yoshimura Y, Touhara K, Misaka T, Minokoshi Y, Nakajima KI.
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Journal Title
Nature communications
Volume: 10
Pages: 1-14
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat.2018
Author(s)
Okamoto S, Sato T, Tateyama M, Kageyama H, Maejima Y, Nakata M, Hirako S, Matsuo T, Kyaw S, Shiuchi T, Toda C, Sedbazar U, Saito K, Asgar NF, Zhang B, Yokota S, Kobayashi K, Foufelle F, Ferré P, Nakazato M, Masuzaki H, Shioda S, Yada T, Kahn BB, Minokoshi Y.
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Journal Title
Cell Reports
Volume: 22
Pages: 706-721
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Gamma-aminobutyric acid signaling in brown adipose tissue promotes systemic metabolic derangement in obesity.2018
Author(s)
Ikegami R, Shimizu I, Sato T, Yoshida Y, Hayashi Y, Suda M, Katsuumi G, Li J, Wakasugi T, Minokoshi Y, Okamoto S, Hinoi E, Nielsen S, Jespersen NZ, Scheele C, Soga T, Minamino T
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Journal Title
Cell Rep.
Volume: 24
Pages: 2827-2837
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Activation of SF1 Neurons in the Ventromedial Hypothalamus by DREADD Technology Increases Insulin Sensitivity in Peripheral Tissues.2017
Author(s)
Coutinho EA, Okamoto S, Ishikawa AW, Yokota S, Wada N, Hirabayashi T, Saito K, Sato T, Takagi K, Wang CC, Kobayashi K, Ogawa Y, Shioda S, Yoshimura Y, Minokoshi Y
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Journal Title
Curr Pharm Des.
Volume: 66
Pages: 2372-2372
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] A combination of high fat diet and nicotine enhances CB1 endocannabinoid receptor in hypothalamic nuclei in mice.2020
Author(s)
Tingting Guo, Mami Matsumoto, Takashi Yagi, Hiroyuki Koyama, Daisuke Aotani, Kazunobu Sawamoto, Yasuhiko Minokoshi, Hiroaki Masuzaki, Noboya Inagaki, Kazuwa Nakao, Tomohiro Tanaka
Organizer
The 97th Annual Meeting of the Physiological Society of Japan
Related Report
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[Presentation] Hypothalamic neuronal circuits regulating hunger-induced taste modification.2019
Author(s)
Ou Fu, Yu Iwai, Masataka Narukawa, Takumi Misaka, Kentaro Ishii, Ken Murata, Kazushige Touhara, Ayako Ishikawa, Yumiko Yoshimura, Yasuhiko Minokoshi, Ken-ichiro Nakajima
Organizer
NIPS International Workshop
Related Report
Int'l Joint Research
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