Mechanism of high fat diet-induced hyperglycemia in obesity-resistant mice

• Project/Area Number: 23700900
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits, studies on eating habits
• Research Institution: Chiba University
• Principal Investigator: LEE Eun Young 千葉大学, 医学(系)研究科(研究院), 助教 (60583424)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: インスリン / 高脂肪食 / 糖尿病 / 脂肪分解 / 糖新生

Research Abstract

High fat diet (HFD) triggers the onset of diabetes mellitus. However, its mechanism remains mostly unknown. We found that insulin receptor mutant mice develop overt hyperglycemia under HFD condition and examined its molecular mechanism. Our analyses revealed that lipolysis in white adipose tissues is increased in the mice, leading to the increased glycerol release and that the upregulation of gluconeogensis in liver results in the occurrence of hyperglycemia.

Research Products

• [Journal Article] Cephalic phase insulin secretion is KATP channel-independent (2013)
  • Author(s): Seino, Y., Miki, M., Fujimoto, W., Lee, EY., Takahashi, Y., Minami, K., Oiso, Y., Seino, S.
  • Journal Title: J Endocrinol Volume: 218(1) Pages: 25-33
  • Peer Reviewed
• [Journal Article] Cephalic phase insulin secretion is KATP channel-independent. (2013)
  • Author(s): Seino, Y., Miki, M., Fujimoto, W., Lee, EY., Takahashi, Y., Minami, K., Oiso, Y., Seino, S.
  • Journal Title: J Endocrinol Volume: 218 Issue: 1 Pages: 25-33
  • DOI: 10.1530/joe-12-0579
  • Peer Reviewed
• [Journal Article] Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar versus non-nutritive sweetener (2012)
  • Author(s): Sakurai, K., Lee, EY., Morita, A., Kimura, S., Kawamura, H., Kasamatsu, A.,Shiiba, M., Yabe, D., Yokote,K., Miki, T.
  • Journal Title: J Diabetes Invest Volume: 3 Pages: 156-63
  • Peer Reviewed
• [Journal Article] Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar versus non-nutritive sweetener (2012)
  • Author(s): Sakurai, K., Lee, EY., Morita, A., Kimura, S., Kawamura, H., Kasamatsu, A.,Shiiba, M., Yabe, D., Yokote,K., Miki, T
  • Journal Title: J Diabetes Invest Volume: 3 Issue: 2 Pages: 156-63
  • DOI: 10.1111/j.2040-1124.2011.00163.x
  • Peer Reviewed
• [Journal Article] Beneficial effects of ventromedial hypothalamus (VMH) lesioning on function and morphology of the liver after hepatectomy in rats (2011)
  • Author(s): Lee, EY., Inoue, S., Senoo, A.,Shimizu, H., Suzuki Y., Ishizuka, N., Imazeki, N., Sasaki, K., Kako, M., Osaka, T., Miki, T.
  • Journal Title: Brain Res Volume: 1421 Pages: 82-9
  • Peer Reviewed
• [Journal Article] Beneficial effects of ventromedial hypothalamus (VMH) lesioning on function and morphology of the liver after hepatectomy in rats. (2011)
  • Author(s): Lee EY, et al.
  • Journal Title: Brain Res Volume: 1421 Pages: 82-89
  • Peer Reviewed
• [Presentation] Unsuppressed Lipolysis in Adipose Tissue by Insulin Is Critical for Glucose Homeostasis under High Fat Diet (2013)
  • Author(s): Lee, E-Y., Sakurai, K., Toda,C., Minokoshi, Y., Miki, T.
  • Organizer: 49th EASD Annual Meeting
  • Place of Presentation: Barcelona, Spain
• [Presentation] 高脂肪餌により糖尿病を発症する変異インスリン受容体ノックインマウスの肝臓における遺伝子発現 (2013)
  • Author(s): 櫻井健一、李恩瑛、橘香穂里、石川耕、三木隆司
  • Organizer: 日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] インスリン受容体変異マウスの高脂肪食感受性糖尿病発症のメカニズム (2013)
  • Author(s): 李恩瑛 櫻井健一 戸田知得 箕越靖彦 三木隆司
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] VEGFシグナル阻害はSDTラットにおけるβ細胞傷害と糖尿病発症を抑制する (2013)
  • Author(s): 向英里、太田毅、河村治清、李恩瑛、森田亜州華、笹瀬智彦、稲垣暢也、岩永敏彦、三木隆司
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] VEGFシグナル阻害はSDTラットにおける膵島β細胞障害と糖尿病発症を抑制する (2013)
  • Author(s): 向英里、太田毅、河村治清、笹瀬智彦、李恩瑛、森田亜州華、稲垣暢也、岩永敏彦、三木隆司
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] Enhanced VEGF signaling in islets contributes to β-cell injury and consequential diabetes in SDT rats (2012)
  • Author(s): Mukai, E., Ohta, T., Kawamura, H., Lee, E.Y., Morita, A., Inagaki, N., Iwanaga, T., Miki, T.
  • Organizer: 9th IDF-WPR Congress & 4th AASD Scientific Meeting
  • Place of Presentation: Kyoto, Japan
• [Presentation] Increased gluconeogenesis from glycerol plays a critical role in developing diabetes under high fat diet (2012)
  • Author(s): Lee, EY., Sakurai, K., Toda,C., Yokote, K., Minokoshi, Y, Miki, T.
  • Organizer: the 9th IDF-WPR Congress & 4th AASD Scientific Meeting
  • Place of Presentation: Kyoto, Japan
• [Presentation] SDTラットでは膵島内のVEGFシグナル亢進がβ細胞を障害し糖尿病を引き起こす (2012)
  • Author(s): 向英里、太田毅、河村治清、笹瀬智彦、李恩瑛、森田亜州華、稲垣暢也、岩永敏彦、三木隆司
  • Organizer: 第27回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] Increased gluconeogenesis from glycerol plays a critical role in developing diabetes (2012)
  • Author(s): Lee, EY., Sakurai, K., Toda, C., Yokote, K., Minokoshi, Y., Miki, T.
  • Organizer: AAAD 2012 4th AASD Scientific meeting
  • Place of Presentation: Kyoto
• [Presentation] 健常日本人におけるGLP-1分泌動態の検討 (2011)
  • Author(s): 櫻井健一、李恩瑛、横尾英孝、河村治清、横手幸太郎、三木隆司
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] Effect of an alpha-glucosidase inhibitor acarbose on glucagon-like peptide-1 secretion and postprandial lipid profile (2011)
  • Author(s): Sakurai, K., Lee, EY, Morita, A., Yabe, D., Yokote, K., Miki, T.
  • Organizer: AASD2011 3rd Annual Meeting
  • Place of Presentation: Beijing, China
• [Presentation] Effect of an alpha-glucosidase inhibitor acarbose on glucagon-like peptide-1 secretion and postprandial lipid profile. (2011)
  • Author(s): Sakurai, K et al.
  • Organizer: AASD2011 3rd Annual Meeting
  • Place of Presentation: Bijing, China
• [Presentation] 高脂肪餌により糖尿病を発症する変異インスリン受容体ノックインマウスの肝臓における遺伝子発現
  • Author(s): 櫻井健一、李恩瑛、橘香穂里、石川耕、三木隆司
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Book] 転写因子Dmbx1欠損マウスのやせの病態解析 (2011)
  • Author(s): 李恩瑛,三木隆司
  • Total Pages: 288
  • Publisher: Adiposcience
• [Book] Adipo science (2011)
  • Author(s): 李恩瑛、 三木隆司
  • Total Pages: 288
  • Publisher: 転写因子Dmbx1欠損マウスのやせの病態解析
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/physiol/index.html
• [Remarks] 代謝生理学研究室ホームページ
  • URL: http://www.m.chiba-u.ac.jp/class/physiol/index.html
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/physiol/