Roles of hypothalamic S6 kinase on diabetes

• Project/Area Number: 22790869
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: Saitama Medical University
• Principal Investigator: ONO Hiraku 埼玉医科大学, 医学部, 講師 (10570616)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: エネルギー・糖質代謝異常 / インスリン抵抗性 / インスリン / LKB1 / 肝臓 / PTEN / Akt / 視床下部 / S6キナーゼ / 摂食 / 糖尿病 / AMPK / GSK3 / 糖負荷試験

Research Abstract

(1) The expression of LKB1 in the liver of db/db mouse was decreased compared to the control mouse. LKB1 rescue in db/db mouse liver by expression vector improved glycemic control.(2) Inhibition of PTEN, the upstream regulator of S6 kinase, in the hypothalamic arcuate nucleus by an expression vector suppressed food intake and body weight gain, but this effect was blunted by overfeeding. PTEN inhibition in the arcuate nucleus improved insulin sensitivity independent to body weight.

Research Products

• [Journal Article] Separation of the gluconeogenic and mitochondrial functions of PGC-1αthrough S6 kinase (2011)
  • Author(s): Lustig Y, Ruas JL, Estall JL, Lo JC, Devarakonda S, Laznik D, Choi JH, Ono H, Olsen JV, Spiegelman BM
  • Journal Title: Genes Dev Volume: 25 Issue: 12 Pages: 1232-44
  • DOI: 10.1101/gad.2054711
  • Peer Reviewed
• [Journal Article] Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with IRS-1 and enhances insulin actions and adipogenesis (2011)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 286 Issue: 23 Pages: 20812-20822
  • DOI: 10.1074/jbc.m110.206904
  • Peer Reviewed
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity (2011)
  • Author(s): Ohno H, Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Asano T
  • Journal Title: Am J Physiol Cell Physiol Volume: 300
  • Peer Reviewed
• [Journal Article] 中枢神経のインスリン作用と糖尿病 (2011)
  • Author(s): 小野啓
  • Journal Title: International Review of Diabetes Volume: 3 Pages: 28-31
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity (2011)
  • Author(s): Ohno H, Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Otani Y, Okubo H, Yoneda M, Fukushima T, Kamata H, Nishimura F, Kurihara H, Katagiri H, Oka Y, Asano T
  • Journal Title: Am J Physiol Cell Physiol Volume: 300(5) Issue: 5 Pages: 1047-54
  • DOI: 10.1152/ajpcell.00416.2010
  • Peer Reviewed
• [Journal Article] Effects of telmisartan on insulin resistance in Japanese type 2 diabetic patients (2010)
  • Author(s): Watanabe M, Inukai K, Sumita T, Ikebukuro K, Ito D, Kurihara S, Ono H, Awata T, Katayama S
  • Journal Title: Intern Med Volume: 49 Pages: 1843-7
  • NAID: 130000336862
  • Peer Reviewed
• [Journal Article] Pin1 associates with and induces translocation of CRTC2 to the cytosol, thereby suppressing CRE transcriptional activity (2010)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Horike N, Yoneda M, Ohno H, Kamata H, Tahara H, Isobe T, Nishimura F, Katagiri H, Oka Y, Fukushima T, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 285 Pages: 33018-27
  • Peer Reviewed
• [Journal Article] Macrophage foam cell formation is augmented in serum from patients with diabetic angiopathy (2010)
  • Author(s): Cui X, Kushiyama A, Yoneda M, Nakatsu Y, Guo Y, Zhang J, Ono H, Kanna M, Sakoda H, Ono H, Kikuchi T, Fujishiro M, Shiomi M, Kamata H, Kurihara H, Kikuchi M, Kawazu S, Nishimura F, Asano T
  • Journal Title: Diabetes Res Clin Pract Volume: 87 Pages: 57-63
  • Peer Reviewed
• [Presentation] 視床下部PTEN/Aktの摂食とインスリン感受性に対する影響 (2012)
  • Author(s): 住田崇, 小野啓, 犬飼浩一, 片山茂裕, 粟田卓也
  • Organizer: 第26回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 愛知県
  • Year and Date: 2012-02-18
• [Presentation] ラット視床下部PTEN/Aktの摂食とインスリン感受性に対する影響 (2012)
  • Author(s): 住田崇, 小野啓, 犬飼浩一, 片山茂裕, 粟田卓也
  • Organizer: 第26回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 愛知県産業労働センター(愛知県)
  • Year and Date: 2012-02-18
• [Presentation] 視床下部PTENの摂食およびインスリン感受性調節における役割 (2011)
  • Author(s): 小野啓, 住田崇, 犬飼浩一, 片山茂裕, 粟田卓也
  • Organizer: 第25回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 東京都
  • Year and Date: 2011-11-05
• [Presentation] 視床下部PTENの摂食およびインスリン感受性調節における役割 (2011)
  • Author(s): 小野啓, 住田崇, 犬飼浩一, 片山茂裕, 粟田卓也
  • Organizer: 第25回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 東京大学工学部武田先端知ビル「武田ホール」(東京都)
  • Year and Date: 2011-11-05
• [Presentation] 視床下部PTENの摂食およびインスリン感受性調節における役割 (2011)
  • Author(s): 住田崇, 小野啓, 犬飼浩一, 片山茂裕, 粟田卓也
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 北海道
  • Year and Date: 2011-05-19
• [Presentation] 視床下部PTENの摂食およびインスリン感受性調節における役割 (2011)
  • Author(s): 住田崇, 小野啓, 犬飼浩一, 片山茂裕, 粟田卓也
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌市教育文化会館(北海道)
  • Year and Date: 2011-05-19
• [Presentation] Acute suppression of hypothalamic PTEN reduces food intake and improves insulin resistance (2011)
  • Author(s): Sumita T, Ono H, Inukai K, Awata T, Kayamama S
  • Organizer: 40th Keystone Symposia ; Type 2 Diabetes, Insulin Resistance and Metabolis Dysfunction
  • Place of Presentation: Keystone, Colorado USA
  • Year and Date: 2011-01-16
• [Presentation] Acute suppression of hypothalamic PTEN reduces food intake and improves insulin resistance (2011)
  • Author(s): Takashi Sumita
  • Organizer: 40^<th> Keystone Symposia ; Type 2 Diabetes, Insulin Resistance and Metabolis Dysfunction
  • Place of Presentation: Keystone, Colorado USA
  • Year and Date: 2011-01-16
• [Presentation] Role of Hepatic LKB1 in the pathophysiology of diabetes in obese diabetic mouse. (2010)
  • Author(s): Sumita T, Ono H, Inukai K, Awata T, Katayama S
  • Organizer: FASEB summer research conference
  • Place of Presentation: Kyoto Japan
  • Year and Date: 2010-10-04
• [Presentation] Role of Hepatic LKB1 in the pathophysiology of diabetes in obese diabetic mouse (2010)
  • Author(s): Takashi Sumita
  • Organizer: EASEB summer research conference, AMPK : Central Regulatory System in Metabolism & Growth
  • Place of Presentation: 滋賀県 大津プリンスホテル
  • Year and Date: 2010-10-04
• [Presentation] 肝S6キナーゼの活性化はインスリンの肝糖産生抑制効果を傷害する (2010)
  • Author(s): 住田崇
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山県 岡山全日空ホテル
  • Year and Date: 2010-05-28
• [Presentation] 肝S6キナーゼの活性化はインスリンの肝糖産生抑制効果を傷害する (2010)
  • Author(s): 住田崇, 小野啓, 犬飼浩一, 粟田卓也, 片山茂裕
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山県
  • Year and Date: 2010-05-27