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

胰岛素抵抗对肝细胞癌BMPs相关上皮间质转化的细胞生物学影响

• 批准号: 22790874
• 负责人: KAWAGUCHI Takumi
• 金额: $ 2.5万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790874/
• 关键词: インスリン抵抗性; 肝細胞癌; 肝臓癌; 上皮間葉移行; dipeptidyl deptidase-4; IL-6; glucagon-like peptide-1; dipeptidyl deptidase-4阻害剤; ピオグリタゾン; 糖尿病; tuberin; mTOR; 細胞増殖; インスリン情報伝達経路; HOMA-IR; 2型糖尿病

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.

慢性肝病和胰岛素抵抗患者常发展为肝细胞癌，导致预后不良。近年来，胰岛素抵抗不仅参与心血管疾病的发展，还参与上皮-间质转化，与肿瘤细胞的癌变和恶性潜能有关。尽管在肝癌发生过程中胰岛素抵抗和上皮-间质转化相关的分子机制尚未完全阐明，但在本研究中，我们已经证明白细胞介素-6在胰岛素培养的肝癌细胞系中促进了上皮-间质转化。我们进一步发现，二肽基去肽酶-4抑制剂抑制白细胞介素-6引起的HepG2细胞上皮-间质转化。

项目成果

Total and high molecular weight adiponectin and hepatocellular carcinoma with HCV infection.

• DOI: 10.1371/journal.pone.0026840
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Sumie S;Kawaguchi T;Kuromatsu R;Takata A;Nakano M;Satani M;Yamada S;Niizeki T;Torimura T;Sata M
• 通讯作者: Sata M

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.

肝硬化患者胰岛中胰岛素表达降低和胰腺转录因子 PDX-1 表达增加：使用人体尸检标本的比较研究。

• DOI: 10.1007/s00535-012-0633-9
• 发表时间: 2013
• 期刊: J Gastroenterol.
• 作者: Sakata M;Kawahara A;Kawaguchi T;Akiba J;Taira T;Taniguchi E;Abe M;Koga H;Kage M;Sata M.
• 通讯作者: Sata M.

Sata M. GLP-1R agonist increased glucose uptake and inhibited GSK3β phosphorylation through the AMPK signaling pathways in human hepatocytes.

Sata M. GLP-1R 激动剂通过人肝细胞中的 AMPK 信号通路增加葡萄糖摄取并抑制 GSK3β 磷酸化。

• 发表时间: 2012
• 作者: Itou M;Kawaguchi T;Sakata M;Taniguchi E;Sumie S;Oriishi T;Mitsuyama K;Torimura T;Tsuruta O
• 通讯作者: Tsuruta O

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

支链氨基酸和含锌食物改善慢性肝病患者胰岛素抵抗的作用

• 发表时间: 2011
• 作者: 川口巧;ら
• 通讯作者: ら

Hybrid training of voluntary and electrical muscle contractions reduces steatosis, insulin resistance, and IL-6 levels in patients with NAFLD: a pilot study

• DOI: 10.1007/s00535-011-0378-x
• 发表时间: 2011-06-01
• 期刊: JOURNAL OF GASTROENTEROLOGY
• 影响因子: 6.3
• 作者: Kawaguchi, Takumi;Shiba, Naoto;Sata, Michio
• 通讯作者: Sata, Michio