Disturbance of hepatic function and over nutrition-related diseases

2010 Fiscal Year Final Research Report

• Project/Area Number: 18109008
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: KANEKO Shuichi Kanazawa University, 医学系, 教授 (60185923)
• Co-Investigator(Kenkyū-buntansha): NAKANUMA Yasuni 金沢大学, 医学系, 教授 (10115256)
• Co-Investigator(Renkei-kenkyūsha): HONDA Masao 金沢大学, 保健学系, 教授 (00272980) ; TAKAMURA Toshinari 金沢大学, 医学系, 准教授 (00324111)
• Project Period (FY): 2006 – 2010
• Keywords: ゲノム / 発現制御 / 肝臓 / 栄養 / 生活習慣病 / 糖尿病

Research Abstract

Liver uptakes varieties of nutrients, metabolizes glucose, proteins, lipids, and drugs and systemically delivers the metabolites through blood streams. We have demonstrated that nutrition related diseases such as atherosclerosis, diabetes, cancer, and inflammation are partially caused by the dysfunction of liver which uptakes excess nutrients. We established the concept of the liver related diseases, and showed the fundamental findings for the development of the diagnosis and therapy for the diseased liver.

Research Products

• [Journal Article] A liver-derived secretory protein, selenoprotein P, causes insulin resistance. (2010)
  • Author(s): H Misu, T Takamura, H Takayama, H Hayashi, N Matsuzawa-Nagata, S Kurita, K Ishikura, H Ando, Y Takeshita, T Ota, M Sakurai, T Yamashita, E Mizukoshi, T Yamashita, M Honda, K Miyamoto, T Kubota, N Kubota, T Kadowaki, HJ Kim, IK Lee, Y Minokoshi, Y Saito, K Takahashi, Y Yamada, N Takakura, S Kaneko.
  • Journal Title: Cell Metab 12(5) Pages: 483-495
  • Peer Reviewed
• [Journal Article] Differential interferon signaling in liver lobule and portal area cells under treatment for chronic hepatitis (2010)
  • Author(s): M Honda, M Nakamura, M Tateno, A Sakai, T Shimakami, T Shirasaki, T Yamashita, K Arai, T Yamashita, Y Sakai, S Kaneko.
  • Journal Title: C.J Hepatol 53(5) Pages: 817-826
  • Peer Reviewed
• [Journal Article] Hokuriku Liver Study Group. Differential gene expression profiling in blood from patients with digestive system cancers. (2010)
  • Author(s): M Honda, Y Sakai, T Yamashita, T Yamashita, A Sakai, E Mizukoshi, Y Nakamoto, I Tatsumi, Y Miyazaki, H Tanno, S Kaneko
  • Journal Title: Biochem Biophys Res Commun 400(1) Pages: 7-15
  • Peer Reviewed
• [Journal Article] Hepatocellular Carcinoma : Signal Intensity at Gadoxetic Acid-enhanced MR Imaging-Correlation with Molecular Transporters and Histopathologic Features. (2010)
  • Author(s): A Kitao, Y Zen, O Matsui, T Gabata, S Kobayashi, W Koda, K Kozaka, N Yoneda, T Yamashita, S Kaneko, Y Nakanuma.
  • Journal Title: Radiology 256(3) Pages: 817-826
  • Peer Reviewed
• [Journal Article] Antitumor Effect after Radiofrequency Ablation of Murine Hepatoma Is Augmented by an Active Variant of CC Chemokine Ligand 3/Macrophage Inflammatory Protein-1α. (2010)
  • Author(s): S Kaneko
  • Journal Title: Cancer Res 70(16) Pages: 6556-6565
  • Peer Reviewed
• [Journal Article] Hokuriku Liver Study Group. Hepatic ISG expression is associated with genetic variation in IL28B and the outcome of IFN therapy for chronic hepatitis C. (2010)
  • Author(s): M Honda, A Sakai, T Yamashita, Y Nakamoto, E Mizukoshi, Y Sakai, T Yamashita, M Nakamura, T Shirasaki, K Horimoto, Y Tanaka, K Tokunaga, M Mizokami, S Kaneko
  • Journal Title: Gastroenterology 139(2) Pages: 499-509
  • Peer Reviewed
• [Journal Article] Oncostatin m renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-Fluorouracil by inducing hepatocytic differentiation. (2010)
  • Author(s): T Yamashita, M Honda, K Nio, Y Nakamoto, T Yamashita, H Takamura, T Tani, Y Zen, S Kaneko.
  • Journal Title: Cancer Res 70(11) Pages: 4687-4697
  • Peer Reviewed
• [Journal Article] Enhancement of tumor-specific T cell responses by transcatheter arterial embolization with dendritic cell infusion for hepatocellular carcinoma. (2010)
  • Author(s): S Kaneko
  • Journal Title: Int J Cancer 126(9) Pages: 2164-2174
  • Peer Reviewed
• [Journal Article] Comprehensive gene expression analysis of 5'-end of mRNA identified novel intronic transcripts associated with hepatocellular carcinoma. (2010)
  • Author(s): Y Hodo, SI Hashimoto, M Honda, T Yamashita, Y Suzuki, S Sugano, S Kaneko, K Matsushima.
  • Journal Title: Genomics 95(4) Pages: 217-223
  • Peer Reviewed
• [Journal Article] CD14+monocytes are vulnerable and functionally impaired under ER stress in patients with type 2 diabetes. (2010)
  • Author(s): T Komura, Y Sakai, M Honda, T Takamura, K Matsushima, S Kaneko.
  • Journal Title: Diabetes 59(3) Pages: 634-643
  • Peer Reviewed
• [Journal Article] Altered hepatic gene expression profiles associated with myocardial ischemia. (2010)
  • Author(s): H Ootsuji, M Honda, S Kaneko, S Usui, M Okajima, H Okada, Y Sakai, T Takamura, K Horimoto, M Takamura.
  • Journal Title: Circ Cardiovasc Genet 3(1) Pages: 68-77
  • Peer Reviewed
• [Journal Article] The histological course of nonalcoholic fatty liver disease in Japanese patients : Tight glycemic control, rather than weight reduction, ameliorates liver fibrosis. (2010)
  • Author(s): E Hamaguchi, T Takamura, M Sakurai, E Mizukoshi, Y Zen, Y Takeshita, S Kurita, K Arai, T Yamashita, M Sasaki, Y Nakanuma, S Kaneko.
  • Journal Title: Diabetes Care 33(2) Pages: 284-286
  • Peer Reviewed
• [Journal Article] J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes : an 8-year follow-up of relatively lean Japanese individuals. (2009)
  • Author(s): M Sakurai, K Miura, T Takamura, M Ishizaki, Y Morikawa, K Nakamura, K Yoshita, T Kido, Y Naruse, S Kaneko, H Nakagawa.
  • Journal Title: Diabet Med 26(8) Pages: 753-759
  • Peer Reviewed
• [Journal Article] Palmitate Induces Insulin Resistance in H4IIEC3 Hepatocytes through Reactive Oxygen Species Produced by Mitochondria. (2009)
  • Author(s): S Nakamura, T Takamura, N Matsuzawa-Nagata, H Takayama, H Misu, H Noda, S Nabemoto, S Kurita, T Ota, H Ando, K Miyamoto, S Kaneko.
  • Journal Title: J Biol Chem 284(22) Pages: 14809-14818
  • Peer Reviewed
• [Journal Article] The hepatic circadian clock is preserved in a lipid-induced mouse model of non-alcoholic steatohepatitis. (2009)
  • Author(s): H Ando, T Takamura, N Matsuzawa-Nagata, KR Shima, S Nakamura, M Kumazaki, S Kurita, H Misu, N Togawa, T Fukushima, A Fujimura, S Kaneko.
  • Journal Title: Biochem Biophys Res Commun 380(3) Pages: 684-688
  • Peer Reviewed
• [Journal Article] Middle-aged Japanese women are resistant to obesity-related metabolic abnormalities. (2009)
  • Author(s): M Sakurai, T Takamura, K Miura, S Kaneko, H Nakagawa.
  • Journal Title: Metabolism 58(4) Pages: 456-459
  • Peer Reviewed
• [Journal Article] Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. (2009)
  • Author(s): S Ura, M Honda, T Yamashita, T Ueda, H Takatori, R Nishino, H Sunakozaka, Y Sakai, K Horimoto, S Kaneko.
  • Journal Title: Hepatology 49(4) Pages: 1098-1112
  • Peer Reviewed
• [Journal Article] EpCAM-Positive Hepatocellular Carcinoma Cells Are Tumor-Initiating Cells With Stem/Progenitor Cell Features. (2009)
  • Author(s): T Yamashita, J Ji, A Budhu, M Forgues, W Yang, HY Wang, H Jia, Q Ye, LX Qin, E Wauthier, LM Reid, H Minato, M Honda, S Kaneko, ZY Tang, XW Wang.
  • Journal Title: Gastroenterology 136(3) Pages: 1012-1024
  • Peer Reviewed
• [Journal Article] Clock gene expression in peripheral leucocytes of patients with type 2 diabetes. (2009)
  • Author(s): H Ando, T Takamura, N Matsuzawa-Nagata, KR Shima, T Eto, H Misu, M Shiramoto, T Tsuru, S Irie, A Fujimura, S Kaneko.
  • Journal Title: Diabetologia 52(2) Pages: 329-335
  • Peer Reviewed
• [Journal Article] Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma. (2009)
  • Author(s): T Yamashita, M Honda, H Takatori, R Nishino, H Minato, H Takamura, T Ohta, S Kaneko.
  • Journal Title: J Hepatology 50(1) Pages: 100-110
  • Peer Reviewed
• [Journal Article] Common transcriptional signature of tumor-infiltrating mononuclear inflammatory cells and peripheral blood mononuclear cells in hepatocellular carcinoma patients. (2008)
  • Author(s): Y Sakai, M Honda, H Fujinaga, I Tatsumi, E Mizukoshi, Y Nakamoto, S Kaneko.
  • Journal Title: Cancer Res 68(24) Pages: 10267-10279
  • Peer Reviewed
• [Journal Article] Obesity upregulates genes involved in oxidative phosphorylation in livers of diabetic patients. (2008)
  • Author(s): T Takamura, H Misu, N Matsuzawa-Nagata, M Sakurai, T Ota, A Shimizu, S Kurita, Y Takeshita, H Ando, M Honda, S Kaneko.
  • Journal Title: Obesity (Silver Spring) 16(12) Pages: 2601-2609
  • Peer Reviewed
• [Journal Article] Comparative analysis of proteome and transcriptome in human hepatocellular carcinoma using 2D-DIGE and SAGE. (2008)
  • Author(s): H Minagawa, T Yamashita, M Honda, Y Tabuse, K Kamijo, A Tsugita, S Kaneko.
  • Journal Title: Protein J 27(7-8) Pages: 409-419
  • Peer Reviewed
• [Journal Article] SAGE application in the study of diabetes. (2008)
  • Author(s): T Takamura, H Misu, T Yamashita, S Kaneko.
  • Journal Title: Curr Pharm Biotechnol 9(5) Pages: 392-399
  • Peer Reviewed
• [Journal Article] Optimal amount of monocyte chemoattractant protein-1 enhances antitumor effects of suiside gene therapy against hepatocelluar carcinoma by M1 macrophage activation. (2008)
  • Author(s): T Tsuchiyama, Y Nakamoto, Y Sakai, N Mukaida, S Kaneko.
  • Journal Title: Cancer Sci 99(10) Pages: 2075-2082
  • Peer Reviewed
• [Journal Article] Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity. (2008)
  • Author(s): N Matsuzawa-Nagata, T Takamura, H Ando, S Nakamura, S Kurita, H Misu, T Ota, M Yokoyama, M Honda, K Miyamoto, S Kaneko.
  • Journal Title: Metabolism 57(8) Pages: 1071-1077
  • Peer Reviewed
• [Journal Article] Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis. (2008)
  • Author(s): M Uno, S Kurita, H Misu, H Ando, T Ota, N Matsuzawa-Nagata, Y Kita, S Nabemoto, H Akahori, Y Zen, Y Nakanuma, S Kaneko, T Takamura.
  • Journal Title: Hepatology 48(1) Pages: 109-118
  • Peer Reviewed
• [Journal Article] Olmesartan ameliorates a dietary rat model of non-alcoholic steatohepatitis through its pleiotropic effects. (2008)
  • Author(s): S Kurita, T Takamura, T Ota, N Matsuzawa-Nagata, Y Kita, M Uno, S Nabemoto, K Ishikura, H Misu, H Ando, Y Zen, Y Nakanuma, S Kaneko.
  • Journal Title: Eur J Pharmacol 588(2-3) Pages: 316-324
  • Peer Reviewed
• [Journal Article] Protein expression profile characteristic to hepatocellular carcinoma revealed by 2D-DIGE with supervised learning. (2008)
  • Author(s): R Teramoto, H Minagawa, M Honda, K Miyazaki, Y Tabuse, K Kamijo, T Ueda, S Kaneko.
  • Journal Title: Biochim Biophys Acta 1784(5) Pages: 764-772
  • Peer Reviewed
• [Journal Article] BMI may be better than waist circumference for defining metabolic syndrome in Japanese women. (2008)
  • Author(s): M Sakurai, T Takamura, K Miura, S Kaneko, H Nakagawa.
  • Journal Title: Diabetes Care 31(3) Pages: 12
  • Peer Reviewed
• [Journal Article] Comparative proteomic and transcriptomic profiling of the human hepatocellular carcinoma. (2008)
  • Author(s): H Minagawa, M Honda, K Miyazaki, Y Tabuse, R Teramoto, T Yamashita, R Nishino, H Takatori, T Ueda, K Kamijo, S Kaneko.
  • Journal Title: Biochem Biophys Res Commun 366(1) Pages: 186-192
  • Peer Reviewed
• [Journal Article] Cross talk of tumor necrosis factor-alpha and the renin-angiotensin system in tumor necrosis factor-alpha-induced plasminogen activator inhibitor-1 production from hepatocytes. (2008)
  • Author(s): Y Takeshita, T Takamura, H Ando, E Hamaguchi, A Takazakura, N Matsuzawa-Nagata, S Kaneko.
  • Journal Title: Eur J Pharmacol 579(1-3) Pages: 426-432
  • Peer Reviewed
• [Journal Article] Impact of diabetes mellitus on prognosis of patients infected with hepatitis C virus. (2007)
  • Author(s): Y Kita, E Mizukoshi, T Takamura, M Sakurai, Y Takata, K Arai, T Yamashita, Y Nakamoto, S Kaneko.
  • Journal Title: Metabolism 56(12) Pages: 1682-1288
  • Peer Reviewed
• [Journal Article] Regulation of adiponectin receptor expression in human liver and a hepatocyte cell line. (2007)
  • Author(s): A Shimizu, T Takamura, N Matsuzawa, S Nakamura, S Nabemoto, Y Takeshita, H Misu, S Kurita, M Sakurai, M Yokoyama, Y Zen, M Sasaki, Y Nakanuma, S Kaneko.
  • Journal Title: Metabolism 56(11) Pages: 1478-1485
  • Peer Reviewed
• [Journal Article] Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet. (2007)
  • Author(s): N Matsuzawa, T Takamura, S Kurita, H Misu, T Ota, H Ando, M Yokoyama, M Honda, Y Zen, Y Nakanuma, K Miyamoto, S Kaneko.
  • Journal Title: Hepatology 46(5) Pages: 1392-1403
  • Peer Reviewed
• [Journal Article] Gene expression profiles in peripheral blood mononuclear cells reflect the pathophysiology of type 2 diabetes. (2007)
  • Author(s): T Takamura, M Honda, Y Sakai, H Ando, A Shimizu, T Ota, M Sakurai, H Misu, S Kurita, N Matsuzawa-Nagata, M Uchikata, S Nakamura, R Matoba, M Tanino, K Matsubara, S Kaneko.
  • Journal Title: Biochem Biophys Res Commun 361(2) Pages: 379-384
  • Peer Reviewed
• [Journal Article] Possible role of alpha-cell insulin resistance in exaggerated glucagon responses to arginine in type 2 diabetes. (2007)
  • Author(s): N Tsuchiyama, T Takamura, H Ando, M Sakurai, A Shimizu, K Kato, S Kurita, S Kaneko.
  • Journal Title: Diabetes Care 30(10) Pages: 2583-2587
  • Peer Reviewed
• [Journal Article] Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease. (2007)
  • Author(s): M Sakurai, T Takamura, T Ota, H Ando, H Akahori, K Kaji, M Sasaki, Y Nakanuma, K Miura, S Kaneko.
  • Journal Title: J Gastroenterol 42(4) Pages: 312-317
  • Peer Reviewed
• [Journal Article] Selective estrogen receptor modulator raloxifene-associated aggravation of nonalcoholic steatohepatitis. (2007)
  • Author(s): T Takamura, A Shimizu, H Ando, S Kaneko.
  • Journal Title: Intern Med 46(9) Pages: 579-581
  • Peer Reviewed
• [Journal Article] Pioglitazone in nonalcoholic steatohepatitis. (2007)
  • Author(s): T Ota, T Takamura, S Kaneko.
  • Journal Title: N Engl J Med 356(10) Pages: 1068
  • Peer Reviewed
• [Journal Article] Induction of reactive oxygen species from isolated rat glomeruli by protein kinase C activation and TNF-α stimulation, and effects of a phosphodiesterase inhibitor. (2007)
  • Author(s): N Koike, T Takamura, S Kaneko.
  • Journal Title: Life Sci 80(18) Pages: 1721-1278
  • Peer Reviewed
• [Journal Article] Association of the C825T polymorphism of the G-protein β3 subunit gene with hypertension, obesity, hyperlipidemia, insulin resistance, diabetes, diabetic complications, and diabetic therapies among Japanese. (2007)
  • Author(s): T Hayakawa, T Takamura, T Abe, SKaneko.
  • Journal Title: Metabolism 56(1) Pages: 44-48
  • Peer Reviewed
• [Journal Article] Comment on : Nathan DM, Buse JB, Davidson MB et al. (2006) Management of hyperglycaemia in type 2 diabetes : a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. (2007)
  • Author(s): Takamura, A Shimizu, H Ando, S Kaneko.
  • Journal Title: Diabetologia 50(1) Pages: 229-330
  • Peer Reviewed
• [Journal Article] Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes. (2007)
  • Author(s): H Misu, T Takamura, N Matsuzawa, A Shimizu, T Ota, M Sakurai, H Ando, K Arai, T Yamashita, M Honda, T Yamashita, S Kaneko.
  • Journal Title: Diabetologia 50(2) Pages: 268-277
  • Peer Reviewed
• [Journal Article] Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis. (2007)
  • Author(s): T Ota, T Takamura, S Kurita, N Matsuzawa, Y Kita, M Uno, H Akahori, H Misu, M Sakurai, Y Zen, Y Nakanuma, S Kaneko.
  • Journal Title: Gastroenterology 132(1) Pages: 282-293
  • Peer Reviewed
• [Journal Article] Factors associated with improvement of fasting plasma glucose level by mealtime dosing of a rapid-acting insulin analog in type 2 diabetes. (2007)
  • Author(s): T Takamura, M Sakurai, M Nakamura, A Shimizu, T Ota, H Misu, Y Takeshita, N Tsuchiyama, S Kurita, H Ando, S Kaneko.
  • Journal Title: Diabetes Res Clin Pract 75(3) Pages: 278-284
  • Peer Reviewed
• [Journal Article] Clinical challenges and images in GI.Yersiniaenterocolitica mesenteric adenitis and terminal ileitis. (2006)
  • Author(s): S Kaneko
  • Journal Title: Gastroenterology 131(5) Pages: 1379,1659
  • Peer Reviewed
• [Journal Article] Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathy. (2006)
  • Author(s): H Ando, T Takamura, Y Nagai, S Kaneko.
  • Journal Title: J Diabetes Complications 20(6) Pages: 367-370
  • Peer Reviewed
• [Journal Article] Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C. (2006)
  • Author(s): M Honda, T Yamashita, T Ueda, H T, R Nishino, S Kaneko.
  • Journal Title: Hepatology 44(5) Pages: 1122-1138
  • Peer Reviewed
• [Journal Article] Tumor necrosis factor-alpha-induced production of plasminogen activator inhibitor 1 and its regulation by pioglitazone and cerivastatin in a nonmalignant human hepatocyte cell line. (2006)
  • Author(s): Y Takeshita, T Takamura, E Hamaguchi, A Shimizu, T Ota, M Sakurai, S Kaneko.
  • Journal Title: Metabolism 55(11) Pages: 1464-1472
  • Peer Reviewed
• [Journal Article] Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis. (2006)
  • Author(s): S Kaneko
  • Journal Title: P Natl Acad Sci USA 103(38) Pages: 14098-14103
  • Peer Reviewed
• [Journal Article] Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes. (2006)
  • Author(s): T Kahara, T Takamura, M Sakurai, H Misu, R Usuda, T Hayakawa, Y Nishimura, Y Bando, T Nagaoka, Y Nagai, S Kaneko.
  • Journal Title: Diabetes Res Clin Pract 71(3) Pages: 241-246
  • Peer Reviewed
• [Remarks] ホームページ等
  • URL: http://m-kanazawa.jp/
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