The impact of hyperinsulinemia and tuberin in the development of hepatocellular carcinoma

• Project/Area Number: 19790643
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: Kurume University
• Principal Investigator: KAWAGUCHI Takumi Kurume University, 医学部, 講師 (00320177)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥570,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: 糖尿病学 / 肝細胞癌 / インスリン抵抗性 / tuberin / mTOR / 細胞増殖 / インスリン情報伝達経路 / HOMA-IR / 2型糖尿病 / インスリン / mammalian target of rapamycin / insulin receptor substrate 1 / Akt / 結節性硬化症

Research Abstract

Hyperinsulinemia is frequently seen in patients with hepatocellularcarcinoma (HCC). Since insulin is a growth-promoting hormone, hyperinsulinemia may beinvolved in the development of HCC. In this study, we reveled that insulin may associate with the development of HCC though activation of intracellular molecules related to cell proliferation.

Research Products

• [Journal Article] Pigment epithelium-derived factor inhibits lysosomal degradation of Bcl-xL and apoptosis in HepG2 cells. (2010)
  • Author(s): Kawaguchi T, Yamagishi S, Itou M, Okuda K, Sumie S, Kuromatsu R, Sakata M, Abe M, Taniguchi E, Koga H, Harada M, Ueno T, Sata M.
  • Journal Title: Am J Pathol. 176 Pages: 168-76
  • Peer Reviewed
• [Journal Article] Association of exogenous insulin or sulphonylurea treatment with an increased incidence of hepatoma in patients with hepatitis C virus infection (2010)
  • Author(s): Kawaguchi T, Taniguchi E, Morita Y, Shirachi M, Tateishi I, Nagata E, Sata M.
  • Journal Title: Liver Int. 30 Pages: 479-486
  • Peer Reviewed
• [Journal Article] Association of exogenous insulin or sulphonylurea treatment with an in creased incidence of hepatoma in patients with hepatitis C virus infection (2010)
  • Author(s): Kawaguchi T et al.
  • Journal Title: Liver Int. 30 Pages: 479-486
  • Peer Reviewed
• [Journal Article] Pigment epithelium-derived factor inhibits lysosomal degradation of Bcl-xL and apoptosis in HepG2 cells (2010)
  • Author(s): Kawaguchi T et al.
  • Journal Title: Am J Pathol. 176 Pages: 168-176
  • Peer Reviewed
• [Journal Article] Branched-chain amino acids and pigment epithelium-derived factor: novel therapeutic agents for hepatitis c virus-associated insulin resistance. (2009)
  • Author(s): Kawaguchi T, Yamagishi S, Sata M.
  • Journal Title: Curr Med Chem. 16 Pages: 4843-57
  • Peer Reviewed
• [Journal Article] Thrombocytopenia, an important interfering factor of antiviral therapy and hepatocellular carcinoma treatment for chronic liver diseases. (2009)
  • Author(s): Kawaguchi T, Kurumatsu R, Ide T, Taniguchi E, Itou M, Sakata M, Abe M, Sumie S, Sata M
  • Journal Title: Kurume Med J. 56 Pages: 9-15
  • NAID: 130000168343
  • Peer Reviewed
• [Journal Article] Thrombocytopenia, an important interfering factor of antiviral therapy and hepatocellular carcinoma treatment for chronic liver diseases (2009)
  • Author(s): Kawaguchi T et al.
  • Journal Title: Kurume Med J. 56 Pages: 9-15
  • NAID: 130000168343
  • Peer Reviewed
• [Journal Article] Altered expression of glucagon-like peptide-1 and dipeptidyl peptidase IV in patients with HCV-related glucose intolerance. (2008)
  • Author(s): Itou M, Kawaguchi T, Taniguchi E, Sumie S, Oriishi T, Mitsuyama K, Tsuruta O, Ueno T, Sata M
  • Journal Title: J Gastroenterol Hepatol. 23 Pages: 244-51
  • Peer Reviewed
• [Journal Article] Branched-chain amino acid-enriched supplementation improves insulin resistance in patients with chronic liver disease. (2008)
  • Author(s): Kawaguchi T, Nagao Y, Matsuoka H, Ide T, Sata M
  • Journal Title: Int J Mol Med. 22 Pages: 105-12
  • Peer Reviewed
• [Journal Article] Supplement improves nutrition and stresses caused by examination-associated fasting in patients with liver cirrhosis. (2008)
  • Author(s): Kawaguchi T, Taniguchi E, Itou M, Mutou M, Ibi R, Shiraishi S, Okada T, Uchida Y, Otsuka M, Tonan T, Fujimoto K, Oriishi T, Tanaka S, Takakura M, Sata M
  • Journal Title: Hepatol Res. 38 Pages: 1178-85
  • NAID: 10023920545
  • Peer Reviewed
• [Journal Article] Body cell mass is a useful parameter for assessing malnutrition and severity of disease in non-ascitic cirrhotic patients with hepatocellular carcinoma or esophageal varices. (2008)
  • Author(s): Kawaguchi T, Taniguchi E, Itou M, Ibi R, Okada T, Mutou M, Shiraishi S, Uchida Y, Otsuka M, Umeki Y, Oriishi T, Hayabuchi H, Tanaka S, Takakura M, Sata M
  • Journal Title: Int J Mol Med. 22 Pages: 589-94
  • Peer Reviewed
• [Journal Article] Branched-chain amino acid-enriched supplementation improves insulin resistance in patients with chronic liver disease (2008)
  • Author(s): Kawaguchi T, et.al.
  • Journal Title: Int J Mol Med 22 Pages: 105-112
  • Peer Reviewed
• [Journal Article] Supplement improves nutrition and stresses caused by examination-associated fasting in patients with liver cirrhosis (2008)
  • Author(s): Kawaguchi T, et.al.
  • Journal Title: Hepatol Res 38 Pages: 1178-1185
  • NAID: 10023920545
  • Peer Reviewed
• [Journal Article] Body cell mass is a useful parameter for assessing malnutrition and severity of disease in non-ascitic cirrhotic patients with hepatocellular car cinoma or esophageal varices (2008)
  • Author(s): Kawaguchi T, et.al.
  • Journal Title: Int J Mol Med 22 Pages: 589-594
  • Peer Reviewed
• [Journal Article] Altered expression of glucagon-like peptide-I and dipeptidyI peptidase IV in patients with HCV-related glucose intolerance. (2008)
  • Author(s): Itou M, Kawaguchi T, Taniguchi E, et. al.
  • Journal Title: J Gastroenterol Hepatol. 23 Pages: 244-251
  • Peer Reviewed
• [Presentation] Pigment Epithelium-Derived Factor Suppresses Apoptosis through Lysosomal Degradation of Bcl-xL in HepG2 cells. (2009)
  • Author(s): Kawaguchi T, et al.
  • Organizer: The 60th Annual Meeting of the Association for the Study of Liver Disease
  • Place of Presentation: Boston, Massachusetts, USA
  • Year and Date: 2009-11-01
• [Presentation] Use of exogenous insulin or sulfonylureas is a potential risk factor for heptocellular carcinoma in hepatitis C patients with diabetes mellitus. (2009)
  • Author(s): Kawaguchi T, et al.
  • Organizer: 44th Annual Meeting of the European Association for the Study of the Liver.
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2009-04-02
• [Presentation] USE OF EXOGENOUS INSULIN OR SULFONYLUREA ASSOCIATED WITH AN INCREASED INCIDENCE OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH HEPATITIS C VIRUS INFECTION (2009)
  • Author(s): Kawaguchi T et al.
  • Organizer: 44^<th> Annual Meeting of the European Association for the Study of the Liver
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2009-04-02
• [Presentation] Use of exogenous insulin or sulfonylureas is a potential risk factor for heptocellular carcinoma in hepatitis C patients with diabetes mellitus. (2008)
  • Author(s): Taniguchi E, et al.
  • Organizer: 55th Annual Meeting of American Association for the Study of Liver Diseases
  • Place of Presentation: SanFrancisco, CA, USA
  • Year and Date: 2008-11-01
• [Presentation] Use of exogenous insulin or sulfonylureas is a potential risk factor for heptocellular carcinoma in hepatitis C patients with diabetes mellitus (2008)
  • Author(s): Taniguchi E, Kawaguchi T, Morita Y, Sata M
  • Organizer: American Association for the Study of Liver Diseases's 59th Annual Meeting
  • Place of Presentation: SanFrancisco, USA
  • Year and Date: 2008-11-01
• [Presentation] 体組成計を用いた肝疾患の重傷度評価 (2007)
  • Author(s): 川口巧, ら
  • Organizer: 第11回日本肝臓学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-18
• [Presentation] 体組成計を用いた肝疾患の重傷度評価 (2007)
  • Author(s): 川口, 巧
  • Organizer: 第11回日本肝蔵学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-18