Analysis of therapeutic effects of GLP-1, novel anti妖iabetic medication, on non-allcoholic fatty liver disease and steatohepatitis.

• Project/Area Number: 21590850
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyushu University
• Principal Investigator: KATO Masaki 九州大学, 大学病院, 助教 (60444808)
• Co-Investigator(Kenkyū-buntansha): KOTOH Kazuhiro 九州大学, 大学病院, 講師 (80289579)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 脂肪肝 / 脂肪性肝炎 / GLP-1 / 糖尿病 / インクレチン / NASH / インスリン抵抗性 / DPP-4 / GIP / RT-PCR / HOMA-IR / HepG2細胞

Research Abstract

The mRNA expression levels of GLP-1R and DPP-4 were quantified in the livers with NAFLD patients and compared with normal subjects. The expression levels of both genes were significantly elevated in NAFLD liver. Fatty acids induced the expression of GLP-1R in HepG2 cells. Treatment with GLP-1 in rats fed high fat diet showed suppression of body weight gain and improvement of hepatic steatosis. Markedly elevated expression of fatty acids oxidation enzymes in adipose and muscle tissues were observed in these rats, suggesting new extrapancreatic actions of GLP-1 in these tissues.

Research Products

• [Journal Article] Increased hepatic expression of dipeptidyl peptidase-4 in nonalcoholic fatty liver disease and its association with insulin resistance and glucose metabolism (2012)
  • Author(s): Miyazaki M, Kato M, Tanaka M, Kohjima M, Nakamura K, Enjoji M, Nakamuta M, Kotoh K, Takayanagi R.
  • Journal Title: Mol Med Report Volume: 5 Pages: 729-733
  • DOI: 10.3892/mmr.2011.707
  • Peer Reviewed
• [Journal Article] Effects of insulin resistance and hepatic lipid accumulation on hepatic mRNA expression levels of apoB, MTP, and L-FABP in nonalcoholic fatty liver disease (2011)
  • Author(s): Higuchi N, Kato M, Tanaka M, Miyazaki M, Takao S, Kohjima M, Kotoh K, Enjoji M, Nakamuta M, Takayanagi R.
  • Journal Title: Experimental and Therapeutic Medicine Volume: 2 Issue: 6 Pages: 1077-81
  • DOI: 10.3892/etm.2011.328
  • Peer Reviewed
• [Journal Article] Potential role of BCAA in glucose metabolism through the accelerated induction of the glucose sensing apparatus in the liver (2011)
  • Author(s): Higuchi N, Kato M, et.al.
  • Journal Title: J Cell Biochem. Volume: 112 Pages: 30-38
  • Peer Reviewed
• [Journal Article] NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease. (2010)
  • Author(s): Enjoji M, Kato M, et.al.
  • Journal Title: Lipids Health Dis Volume: 12 Pages: 9-29
  • Peer Reviewed
• [Presentation] GLP-1投与によるNAFLD肝改善メカニズムの解明 (2012)
  • Author(s): 田中紘介、加藤正樹
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢(予定)
  • Year and Date: 2012-06-08
• [Presentation] GLP-1投与によるNAFLD肝の改善メカニズムの解明 (2012)
  • Author(s): 田中紘介、加藤正樹
  • Organizer: 第48回肝臓学会総会
  • Place of Presentation: ホテル日航金沢(金沢)
  • Year and Date: 2012-06-07
• [Presentation] NAFLD症例におけるDPP-4発現の評価 (2010)
  • Author(s): 宮崎将之、樋口野日斗、加藤正樹、古藤和浩、高柳涼一
  • Organizer: 第38回日本肝臓学会東部会
  • Place of Presentation: 東京
  • Year and Date: 2010-12-02
• [Presentation] NAFLDにおけるDPP-4発現の評価 (2010)
  • Author(s): 宮崎将之
  • Organizer: 第38回日本肝臓学会東部会
  • Place of Presentation: 東京都、京王プラザ
  • Year and Date: 2010-12-02
• [Remarks] 九州大学病態制御内科肝臓研究室
  • URL: http://www.med.kyushu-u.ac.jp/intmed3/general3.html#ken