The cytobiological impact of insulin resistance on BMPs-related epithelial-mesenchymal transition of hepatocellular carcinoma

2012 Fiscal Year Final Research Report

• Project/Area Number: 22790874
• 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 久留米大学, 医学部, 講師 (00320177)
• Project Period (FY): 2010 – 2012
• Keywords: インスリン抵抗性 / 肝細胞癌

Research Abstract

Patients with chronic liver disease and insulin resistance frequently develop hepatocellular carcinoma, leading to poor progosis. Recently, insulin resistance is reported to be involved in the development of not only cardio-vascular disease, but also epithelial-mesenchymal transition, which link to carcinogenesis and malignant potential of tumor cells. Although molecular mechanism(s) for an association of insulin resistance and epithelial-mesenchymal transition is not fully elucidated in hepatocarcinogenesis, we have demonstrated that interleukin-6 promoted epithelial-mesenchymal transition in a hepatoma cell line cultured with insulin in this study. We further showed that dipeptidyl deptidase-4 inhibitor suppressed interleukin-6-caused epithelial-mesenchymal transition in HepG2 cells.

Research Products

• [Journal Article] Decreased expression of insulin and increasedexpression of pancreatic transcription factor PDX-1 in islets in patients with liver cirrhosis: a comparative investigation using human autopsy specimens. (2013)
  • Author(s): Sakata M, Kawahara A, Kawaguchi T, Akiba J, Taira T, Taniguchi E, Abe M, Koga H, Kage M, Sata M.
  • Journal Title: J Gastroenterol. Volume: 48 Pages: 277-85
  • DOI: DOI: 10.1007/s00535-012-0633-9
  • Peer Reviewed
• [Journal Article] Sata M. Branched-chain amino acids as pharmacological nutrients in chronic liver disease. (2011)
  • Author(s): Kawaguchi T, Izumi N, Charlton MR
  • Journal Title: Hepatology. Volume: 2;54 Pages: 1063-70
  • DOI: DOI:10.1002/hep.24412.
  • Peer Reviewed
• [Journal Article] Insulin resistance and chronic liver disease. (2011)
  • Author(s): Kawaguchi T, Taniguchi E, Itou M, Sakata M, Sumie S, Sata M.
  • Journal Title: World J Hepatol. Volume: 3 Pages: 99-107
  • DOI: DOI:10.4254/wjh.v3.i5.99.
  • Peer Reviewed
• [Journal Article] Total and high molecular weight adiponectin and hepatocellular carcinoma with HCV infection. (2011)
  • Author(s): Sumie S, Kawaguchi T, Kuromatsu R, Takata A, Nakano M, Satani M, Yamada S, Niizeki T, Torimura T, Sata M.
  • Journal Title: PLoS One. Volume: 6:e Pages: 26840
  • DOI: DOI:10.1371/journal.pone.0026840.
  • Peer Reviewed
• [Journal Article] Hybrid training of voluntary and electrical muscle contractions decreased fasting blood glucose and serum interleukin-6 levels in elderly people: a pilot study. (2011)
  • Author(s): Kawaguchi T, Shiba N, Takano Y, Maeda T, Sata M.
  • Journal Title: Appl Physiol Nutr Metab. Volume: 36 Pages: 276-83
  • DOI: DOI:10.1139/h10-108.
  • Peer Reviewed
• [Journal Article] Hybrid training of voluntary and electrical muscle contractions reduces steatosis, insulin resistance, and IL-6 levels in patients with NAFLD: a pilot study. (2011)
  • Author(s): Kawaguchi T, Shiba N, Maeda T, Matsugaki T, Takano Y, Itou M, Sakata M, Taniguchi E, Nagata K, Sata M.
  • Journal Title: J Gastroenterol. Volume: 46 Pages: 746-57
  • DOI: DOI:10.1007/s00535-011-0378-x.
  • Peer Reviewed
• [Journal Article] The pathogenesis, complications and therapeutic strategy for hepatitis C virus-associated insulin resistance in the era of anti-viral treatment. (2010)
  • Author(s): Kawaguchi T, Taniguchi E, Itou M, Sumie S, Yamagishi S, Sata M.
  • Journal Title: Rev Recent Clin Trials. Volume: 5 Pages: 147-57
  • URL: http://www.eurekaselect.com/86625/a rticle
  • Peer Reviewed
• [Presentation] 肝発癌抑制を目指した耐糖能異常へのアプローチ:C型肝炎におけるインクレチン動態と肝細胞糖取り込みにおけるGLP-1シグナル伝達経路. (2012)
  • Author(s): 川口巧,伊藤実,佐田通夫.
  • Organizer: 第48回日本肝臓学会
  • Place of Presentation: 金沢市,石川県
  • Year and Date: 2012-06-07
• [Presentation] Sata M. GLP-1R agonist increased glucose uptake and inhibited GSK3β phosphorylation through the AMPK signaling pathways in human hepatocytes. (2012)
  • Author(s): Itou M, Kawaguchi T, Sakata M, Taniguchi E, Sumie S, Oriishi T, Mitsuyama K, Torimura T, Tsuruta O
  • Organizer: Digestive Disease Week2012.
  • Place of Presentation: San Diego, California, USA.
  • Year and Date: 2012-05-19
• [Presentation] 慢性肝疾患患者におけるBCAA・亜鉛含有食品のインスリン抵抗性改善効果. (2011)
  • Author(s): 川口巧,長尾由実子,井出達也,佐田通夫.
  • Organizer: 第15回日本肝臓学会大会.
  • Place of Presentation: 福岡市,福岡県.
  • Year and Date: 2011-10-20
• [Presentation] HCV関連肝細胞癌と糖尿病治療薬の関連. (2011)
  • Author(s): 川口巧,谷口英太郎,佐田通夫.
  • Organizer: 第15回日本肝臓学会大会.
  • Place of Presentation: 福岡市,福岡県.
  • Year and Date: 2011-10-20
• [Presentation] Hybrid-training of voluntary and electrical muscle contractions improves nonalcoholic fatty liver disease and reduces insulin resistance and interleukin-6 levels. (2010)
  • Author(s): Kawaguchi T, Shiba N, Maeda T, Matsugaki T, Takano Y, Itou M, Sakata M, Taniguchi E, Nagata K, Sata M.
  • Organizer: The 61st Annual Meeting of the American Association for the Study of the Liver Disease.
  • Place of Presentation: Boston, Massachusetts, USA.
  • Year and Date: 2010-10-30