Project/Area Number |
20590761
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | The University of Tokyo |
Principal Investigator |
TOMIYA Tomoaki The University of Tokyo, 医学部附属病院, 特任講師 (90227637)
|
Co-Investigator(Kenkyū-buntansha) |
IKEDA Hitoshi 東京大学, 医学部附属病院, 准教授 (80202422)
|
Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
Keywords | 再生医学 / 栄養学 / 内科 / トランスレイショナルリサーチ / トランスレーショナルリサーチ / 生理活性 |
Research Abstract |
Insulin-like growth factor I (IGF-I) plays an important role in growth, metabolism, survival and oxidative stress of various types of cells. IGF-I is produced predominantly by the liver, especially by hepatocytes. Serum IGF-I levels are decreased in patients with liver cirrhosis. Supplementation of IGF-I induces the improvement of liver function in patients with liver cirrhosis. In this study, we examined stimulatory effect of amino acids on IGF-I production by hepatocytes, and the effect of IGF-I on hepatocyte growth and function to investigate the possibility that amino acid administration improves liver function in patients with liver cirrhosis. Among various amino acids, branched-chain amino acids, especially leucine, increased IGF-I production by rat primary cultured hepatocytes. Addition of IGF-I stimulated proliferation, protein production and glucose metabolism by rat hepatocytes. In these cells, mTOR dependent signaling pathway was up-regulated. The stimulatory effect of IGF-I was abrogated by the addition of an inhibitor of mTOR pathway. These observations suggest that IGF-I stimulates hepatocyte function directly, and stimulation of IGF-I production is a possible therapeutic candidate in patients with liver cirrhosis.
|