Regulations of Hepatic and pancreatic autonomic nerves by leptin and application to improvement of glucose metabolism

• Project/Area Number: 26870672
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology); Metabolomics
• Research Institution: Kanazawa Medical University
• Principal Investigator: TANIDA Mamoru 金沢医科大学, 医学部, 講師 (70512309)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed(Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost : ¥3,100,000、Indirect Cost : ¥930,000); Fiscal Year 2015 : ¥2,210,000 (Direct Cost : ¥1,700,000、Indirect Cost : ¥510,000); Fiscal Year 2014 : ¥1,820,000 (Direct Cost : ¥1,400,000、Indirect Cost : ¥420,000)
• Keywords: 自律神経 / レプチン / 糖代謝 / 肝臓 / 視床下部 / 細胞内シグナル伝達 / 糖尿病 / 血糖調節 / 遺伝子組換えマウス

Outline of Final Research Achievements

Diabetes mellitus is one of serious health problem. In this experiment, we used animals and examined effects of leptin, appetite suppressor, on autonomic nerves to the liver and the pancreas which play an important role in regulating glucose metabolism, and cleared possible role of leptin in diabetes therapy. We showed that leptin stimulated liver autonomic nerves through the hypothalamic molecular signals. Thus, our evidence suggest that leptin may be useful reagent for diabetes treatment via the brain.

Research Products

• [Int'l Joint Research] アイオワ大学(アメリカ合衆国)
• [Journal Article] Protein Tyrosine Phosphatase δ mediates the Sema3A-induced cortical basal dendritic arborization through the activation of Fyn tyrosine kinase. (2017)
  • Author(s): Nakamura F, Okada T, Shishikura M, Uetani N, Taniguchi M, Yagi T, Iwakura Y, Ohshima T, Goshima Y, Strittmatter S.
  • Journal Title: The Journal of Neuroscience Volume : 37 Pages : 7125-7139
  • DOI: 10.1523/jneurosci
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The responses of pulmonary and systemic circulation and airway to anaphylactic mediators in anesthetized BALB/c mice. (2016)
  • Author(s): Wang M, Shibamoto T, Kuda Y, Tanida M, Zhang T, Song J, Kurata Y.
  • Journal Title: Life Sciences Volume : 147 Pages : 77-84
  • DOI: 10.1016/j.lfs.2016.01.034
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Simvastatin and atorvastatin facilitates amyloid β-protein degradation in extracellular spaces by increasing neprilysin secretion from astrocytes through activation of MAPK/Erk1/2 pathways. (2016)
  • Author(s): Yamamoto, N., Fujii, Y., Kasahara, R., Tania, M., Ohora, K., Ono, Y., Suzuki, K. and Sobue, K.
  • Journal Title: Glia Volume : 64 Pages : 952-962
  • DOI: 10.1002/glia.22974
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Centra insulin-action activates Kupffer cells by suppressing hepatic vagal activation through nicotinic alpha 7 acetylcholine receptor. (2016)
  • Author(s): Kimura K, Tanida M, Nagata N, Inaba Y, Watanabe H, Nagashimada M, Ota T, Asahara S, Kido Y, Matsumoto M, Toshinai K, Nakazato M, Shibamoto T, Kaneko S, Kasuga M, Inoue H
  • Journal Title: Cell reports Volume : 14 Pages : 2362-2374
  • DOI: 10.1016/j.celrep.2016.02.032
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intragastric injection of Lactobacillus casei strain Shirota suppressed spleen sympathetic activation by central corticotrophin-releasing factor or peripheral 2-deoxy-d-glucose in anesthetized rats. (2016)
  • Author(s): Tanida M, Takada M, Kato-Kataoka A, Kawai M, Miyazaki K, Shibamoto T.
  • Journal Title: Neuroscience Letters Volume : 619 Pages : 114-120
  • DOI: 10.1016/j.neulet.2016.03.016
  • Peer Reviewed
• [Journal Article] The Responses of Pulmonary and Systemic Circulation and Airway to Allergic Mediators in Anesthetized Rats. (2016)
  • Author(s): Wang M, Shibamoto T, Kuda Y, Tanida M, Zhang T, Song J, Mukai K, Kurata Y.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume : 39 Pages : 556-563
  • DOI: 10.1248/bpb.b15-00864
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Role of Lumbar Sympathetic Nerves in Regulation of Blood Flow to Skeletal Muscle during Anaphylactic Hypotension in Anesthetized Rats. (2016)
  • Author(s): Song J, Tanida M, Shibamoto T, Zhang T, Wang M, Kuda Y, Kurata Y
  • Journal Title: PLoS One Volume : 11
  • DOI: 10.1371/journal.pone.0150882
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP). (2015)
  • Author(s): hibasaki Y, Hayata-Takano A, Hazama K, Nakazawa T, Shintani N, Kasai A, Nagayasu K, Hashimoto R, Tanida M, Katayama T, Matsuzaki S, Yamada K, Taniike M, Onaka Y, Ago Y, Waschek JA, Köves K, Reglődi D, Tamas A, Matsuda T, Baba A, Hashimoto H.
  • Journal Title: Neuroscience Volume : 297 Pages : 95-104
  • DOI: 10.1016/j.neuroscience.2015.03.062
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] L-Ornithine intake affects sympathetic nerve outflows and reduces body weight and food intake in rats. (2015)
  • Author(s): Konishi Y, Koosaka Y, Maruyama R, Imanishi K, Kasahara K, Matsuda A, Akiduki S, Hishida Y, Kurata Y, Shibamoto T, Satomi J, Tanida M.
  • Journal Title: Brain Research Bulletin Volume : 111 Pages : 48-52
  • DOI: 10.1016/j.brainresbull.2014.11.004
  • Peer Reviewed
• [Journal Article] Possible role of afferent autonomic signals in abdominal organs in anorexic and cardiovascular responses to nicotine injection in rats. (2015)
  • Author(s): Yagi S, Tanida M, Satomi J.
  • Journal Title: Neuroreport Volume : 26 Pages : 445-449
  • DOI: 10.1097/wnr.0000000000000361
  • Peer Reviewed
• [Journal Article] Pulmonary vascular and airway responses to systemic vasoconstrictors in anesthetized BALB/c mice (2015)
  • Author(s): Wang M, Shibamoto T, Shinomiya S, Yamamoto Y, Kurata Y, Kuda Y, Tanida M, Toga H
  • Journal Title: Journal of Cardiovascular Pharmacology Volume : 65 Pages : 325-334
  • DOI: 10.1097/fjc.0000000000000199
  • Peer Reviewed
• [Journal Article] Systemic vasoconstriction modulates the responses of pulmonary vasculature and airway to vasoconstrictors in anesthetized rats. (2015)
  • Author(s): Wang M, Shibamoto T, Kuda Y, Tanida M, Kurata Y.
  • Journal Title: Experimental Lung Research Volume : 41 Pages : 324-334
  • DOI: 10.3109/01902148.2015.1032448
  • Peer Reviewed
• [Journal Article] Hypothalamic Nesfatin-1 Stimulates Sympathetic Nerve Activity via Hypothalamic ERK Signaling. (2015)
  • Author(s): Tanida, M., Gotoh, H., Yamamoto, N., Wang, M., Kuda, Y., Kurata, Y., Mori, M., Shibamoto, T.
  • Journal Title: Diabetes Volume : 64 Pages : 3725-3736
  • DOI: 10.2337/db15-0282
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Possible role of afferent autonomic signals in abdominal organs in anorexic and cardiovascular responses to nicotine injection in rats. (2015)
  • Author(s): Yagi S, Tanida M, Satomi J
  • Journal Title: Neuroreport Volume : 印刷中
  • Peer Reviewed
• [Journal Article] Leptin receptor signaling in the hypothalamus regulates hepatic autonomic nerve activity via phosphatidylinositol 3-kinase and AMP-activated protein kinase. (2015)
  • Author(s): Tanida M, Yamamoto N, Morgan DA, Kurata Y, Shibamoto T, Rahmouni K.
  • Journal Title: J Neurosci. Volume : 35 Pages : 4747-484
  • DOI: 10.1523/jneurosci.1828-14.2015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of anesthetics on the renal sympathetic response to anaphylactic hypotension in rats. (2014)
  • Author(s): Sun L, Tanida M, Wang M, Kuda Y, Kurata Y, Shibamoto T.
  • Journal Title: Plos One Volume : 9
  • DOI: 10.1371/journal.pone.0113945
  • Peer Reviewed / Open Access
• [Journal Article] Mouse anaphylactic shock is caused by reduced cardiac output, but not by systemic vasodilatation or pulmonary vasoconstriction, via PAF and histamine. (2014)
  • Author(s): Wang M, Shibamoto T, Tanida M, Kuda Y, Kurata Y.
  • Journal Title: Life Sciences Volume : 116 Pages : 98-105
  • DOI: 10.1016/j.lfs.2014.09.010
  • Peer Reviewed
• [Journal Article] Leptin inhibits amyloid β-protein fibrillogenesis by decreasing GM1 gangliosides on the neuronal cell surface through PI3K/Akt/mTOR pathway. (2014)
  • Author(s): Yamamoto N, Tanida M, Kasahara R, Sobue K, Suzuki K
  • Journal Title: J Neurochem Volume : 131 Pages : 323-32
  • DOI: 10.1111/jnc.12828
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Olfactory stimulatory with grapefruit and lavender oils change autonomic nerve activity and physiological function. (2014)
  • Author(s): Nagai K, Niijima A, Horii Y, Shen J, Tanida M.
  • Journal Title: Autonomic Neuroscience: Basic and Clinical Volume : 185 Pages : 29-35
  • DOI: 10.1016/j.autneu.2014.06.005
  • Peer Reviewed
• [Journal Article] Injection of Lactobacillus casei strain Shirota affects autonomic nerve activities in a tissue-specific manner, and regulates glucose and lipid metabolism in rats. (2014)
  • Author(s): Tanida M, Imanishi K, Akashi H, Kurata Y, Chonan O, Naito E, Kunihiro S, Kawai M, Kato-Kataoka A, Shibamoto T.
  • Journal Title: Journal of Diabetes Investigation Volume : 5 Pages : 153-161
  • DOI: 10.1111/jdi.12141
  • Peer Reviewed
• [Journal Article] Angiotensin II and vasopressin are involved in the defense system against anaphylactic hypotension in anesthetized rats. (2014)
  • Author(s): Wang M, Shibamoto T, Kuda Y, Sun L, Tanida M, Kurata Y.
  • Journal Title: Eur J Pharmacol. Volume : 731 Pages : 38-43
  • DOI: 10.1016/j.ejphar.2014.03.012
  • Peer Reviewed
• [Journal Article] Soy isoflavone affects the autonomic nervous system in a tissue-specific manner in anesthetized rats (2014)
  • Author(s): Tanida M, Imanishi K, Komatsu M, Satomi J, Yamamoto N, Wang M, Kurata Y, Shibamoto T.
  • Journal Title: Experimental Biology and Medicine Volume : 239 Pages : 477-483
  • DOI: 10.1177/1535370213519197
  • Peer Reviewed
• [Journal Article] Leptin inhibits amyloid β-protein degradation through decrease of neprilysin expression in primary cultured astrocytes. (2014)
  • Author(s): Yamamoto N,Tanida M,Ono Y,Kasahara R,Fujii Y,Ohora K,Suzuki K,Sobue K
  • Journal Title: Biochem Biophys Res Commun Volume : 445 Pages : 214-7
  • DOI: 10.1016/j.bbrc.2014.01.168
  • Peer Reviewed / Open Access
• [Presentation] 摂食調節因子 nesfatin-1 による自律神経を介する循環調節機構 (2016)
  • Author(s): 谷田 守
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-03-22
• [Presentation] レプチンによる肝臓自律神経調節における視床下部弓状核の役割 (2015)
  • Author(s): 谷田 守、芝本 利重
  • Organizer: 第36回日本肥満学会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-02
• [Presentation] GLP1脳室内投与によるマウス自律神経調節と高脂肪食性肥満マウスへの作用 (2015)
  • Author(s): 谷田 守、九田裕一、倉田康孝、芝本利重
  • Organizer: 第25回日本病態生理学会大会
  • Place of Presentation: 愛媛大学（愛媛県・松山市）
  • Year and Date: 2015-07-31
• [Presentation] アルコール投与がアナフィラキシー低血圧時の腎臓交感神経活動へ及ぼす影響 (2015)
  • Author(s): 谷田 守、王 墨飛、宋 潔、九田 裕一、倉田 康孝、芝本 利重
  • Organizer: 第36回日本循環制御医学会総会
  • Place of Presentation: ウインクあいち（愛知県・名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] アナフィラキシー低血圧時の血圧と腎臓交感神経応答に対するアルコール投与の影響 (2015)
  • Author(s): 谷田 守、芝本 利重
  • Organizer: 第30回日本Shock学会総会
  • Place of Presentation: 京王プラザホテル八王子（東京都・八王子市）
  • Year and Date: 2015-05-22
• [Presentation] GLP-1によるマウス自律神経調節の視床下部分子メカニズム (2015)
  • Author(s): 谷田守、九田裕一、倉田康孝、芝本利重
  • Organizer: 第92回日本生理学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] GLP-1のマウス脳室内投与による交感神経系促進の細胞内シグナリング (2014)
  • Author(s): 谷田守、芝本利重
  • Organizer: 第35回日本肥満学会
  • Place of Presentation: シーガイアコンベンションセンター（宮崎県宮崎市）
  • Year and Date: 2014-10-24 – 2014-10-25
• [Presentation] ラットアナフィラキシーショックにおける腎臓交感神経活動の反応と麻酔薬の影響 (2014)
  • Author(s): 谷田守、孫玲玲、芝本利重
  • Organizer: 第24回日本病態生理学会
  • Place of Presentation: 北九州国際会議場（福岡県北九州市）
  • Year and Date: 2014-08-08 – 2014-08-10
• [Presentation] アナフィラキシーショクにおけるラット腎臓交感神経活動の反応と麻酔薬の影響 (2014)
  • Author(s): 谷田守
  • Organizer: 第29回日本Shock学会総会
  • Place of Presentation: 松山市コミュニティーセンター（愛媛県松山市）
  • Year and Date: 2014-05-16 – 2014-05-17
• [Book] Imidazole Dipeptides: Food and Nutritional Components in Focus No. 8Carnosine and the control of blood glucose (2015)
  • Author(s): Okumura N, Tanida M, Niijima A, Tsuruoka N, Kiso Y, Nagai K
  • Total Pages: 19
  • Publisher: Royal Society of Chemistry
• [Remarks] 金沢医科大学 生理学２講座
  • URL: http://medicine-physiol2.kanazawa-med.labos.ac/one/