Analysis of interaction between amino acids and pancreatic beta cell mass via epigenetic modulation.

• Project/Area Number: 24700826
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits, studies on eating habits
• Research Institution: Kobe University
• Principal Investigator: ASAHARA Shun-ichiro 神戸大学, 医学(系)研究科(研究院), 研究員 (00570342)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: エピジェネティクス / 2型糖尿病

Research Abstract

In addition to genetic factors, a recent shift towards the western diet may increase the number of type 2 diabetes patients in Japan. Dietary fat intake is apparently increasing for the Japanese population. Furthermore, we focused on the importance of amino acids intake. Therefore we examined the relationship between pancreatic beta cell failure and amino acids.
We analyzed the amino acids concentration in pancreatic islets of mice fed high fat diet. The results revealed that the amino acids concentration in pancreatic islets of high fat diet feeding mice was lower than normal chow diet feeding mice. We found that Serine, Isoleucine and Histidine were largely lower in pancreatic islets of high fat fed mice, so we cultured INS-1 cells with serine, isoleucine and histidine free medium. That resulted in the suppression of mTORC1 activity in INS-1 cells and the reduction of INS-1 cells viability.

Research Products

• [Journal Article] Pancreaticβcell failure mediated by mTORC1 hyperactivity and autophagic impairment (2014)
  • Author(s): Bartolomé A, Kimura-Koyanagi M, Asahara S, Guillén C, Inoue H, Teruyama K, Shimizu S, Kanno A, García-Aguilar A, Koike M, Uchiyama Y, Benito M, Noda T, Kido Y
  • Journal Title: Diabetes Volume: (in press)
  • Peer Reviewed
• [Journal Article] Contribution of insulin signaling to the regulation of pancreatic beta-cell mass during the catch-up growth period in a low birth weight mouse model (2014)
  • Author(s): Yoshida Y, Fuchita M, Kimura-Koyanagi M, Kanno A, Matsuda T, Asahara S, Hashimoto N, Isagawa T, Ogawa W, Aburatani H, Noda T, Seino S, Kasuga M, Kido Y
  • Journal Title: Diabetology International Volume: 5 Pages: 43-52
  • Peer Reviewed
• [Journal Article] Pancreatic β cell failure mediated by mTORC1 hyperactivity and autophagic impairment. (2014)
  • Author(s): Bartolome A, Kimura-Koyanagi M, Asahara SI, Guillen C, Inoue H, Teruyama K, Shimizu S, Kanno A, Garcia-Aguilar A, Koike M, Uchiyama Y, Benito M, Noda T, Kido Y
  • Journal Title: Diabetes Volume: 未定 Issue: 9 Pages: 2996-3008
  • DOI: 10.2337/db13-0970
  • NAID: 40020504710
  • Peer Reviewed / Open Access
• [Journal Article] Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin (2013)
  • Author(s): Asahara S, Shibutani Y, Teruyama K, Inoue H, Kawada Y, Etoh H, Matsuda T, Kimura-Koyanagi M, Hashimoto N, Sakahara M, Fujimoto W, Takahashi H, Ueda S, Hosooka T, Satoh T, Inoue H, Matsumoto M, Aiba A, Kasuga M, Kido Y
  • Journal Title: Diabetologia Volume: 56 Pages: 1088-1097
  • Peer Reviewed
• [Journal Article] Histidine augments the suppression of hepatic glucose production by central insulin action. (2013)
  • Author(s): Kimura K, Nakamura Y, Inaba Y, Matsumoto M, Kido Y, Asahara S, Matsuda T, Watanabe H, Maeda A, Inagaki F, Mukai C, Takeda K, Akira S, Ota T, Nakabayashi H, Kaneko S, Kasuga M, Inoue H.
  • Journal Title: Diabetes Volume: 62 Issue: 7 Pages: 2266-77
  • DOI: 10.2337/db12-1701
  • Peer Reviewed
• [Presentation] 2型糖尿病感受性遺伝子GCN2は膵β細胞量の調節に関与する (2013)
  • Author(s): 神野歩、吉冨理紗、増田勝久、淺原俊一郎、松田友和、木村真希、渋谷由紀、春日雅人、清野進、木戸良明
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2013-05-16
• [Presentation] 2型糖尿病感受性遺伝子GCN2は膵β細胞量の調節に関与する (2013)
  • Author(s): 神野歩、吉冨理紗、増田勝久、淺原俊一郎、松田友和、木村真希、渋谷由紀、春日雅人、清野進、木戸良明
  • Organizer: 第28回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 宮崎
  • Year and Date: 2013-02-14
• [Presentation] Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β -cell mass via epigenetic modification of Cdkn1c (2013)
  • Author(s): Asahara S
  • Organizer: Beta Cell Workshop 2013
  • Place of Presentation: 京都
• [Presentation] 2型糖尿病発症におけるelF2αキナーゼGCN2の機能解析 (2012)
  • Author(s): 吉冨理紗、神野歩、淺原俊一郎、松田友和、木村真希、渋谷由紀、春日雅人、清野進、木戸良明
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-12
• [Presentation] 2型糖尿病発症におけるeIF2αキナーゼGCN2の機能解析 (2012)
  • Author(s): 神野歩、吉冨理紗、淺原俊一郎、松田友和、木村真希、渋谷由紀、春日雅人、清野進、木戸良明
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2012-05-19
• [Presentation] 膵β細胞におけるインスリンシグナルのエピジェネティクス制御の解析
  • Author(s): 川田有希奈、淺原俊一郎、佐藤綾香、橋本尚子、清野進、木戸良明
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本ホテルキャッスル
• [Presentation] Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β-cell mass via epigenetic modification of Cdkn1c
  • Author(s): Asahara SI, Etoh H, Inoue H, Teruyama K, Shibutani Y, Ihara Y, Bartolome A, Hashimoto N, Matsuda T, Kimura-Koyanagi M, Kanno A, Nagashima K, Nishimura W, Yasuda K, Inagaki N, Seino S, Kasuga M, Kido Y
  • Organizer: 5th AASD
  • Place of Presentation: グランドヒルトンソウル
• [Remarks]
  • URL: http://www.research.kobe-u.ac.jp/fhs-diabetes/