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Organismal Biosystems Laboratories Medicine and Pathophysiology Group (Prof. Shimomura)
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Laboratory of Biocatalysis Science

Collaborative institutes
Laboratory of Immune Regulation Chugai Pharmaceutical CO.,LTD.
Optical Nano Device Group
OMRON Corporation


  1. Shimomura, I., Funahashi, T., Takahashi, M., Maeda, K., Kotani, K., Nakamura, T., Yamashita, S., Miura, S., Fukuda, Y., Takemura, K., Tokunaga, T., and Matsuzawa, Y. (1996) Enhanced expression of PAI-1 in visceral fat: Possible contributor to vascular disease in obesity. Nature Medicine 2, 800-803.

  2. Shimomura, I., Takahashi, M., Tokunaga, K., Keno, Y., Nakamura, T., Yamashita, S., Takemura, K., Yamamoto, T., Funahashi, T., and Matsuzawa, Y. (1996) Rapid enhancements of acyl-CoA synthetase, LPL, and Glut-4 mRNA in adipose tissue of VMH rats. Am. J. Physiol. 270, E995-1002.

  3. Shimomura, I., Shimano, H., Horton, J. D., Goldstein, J. L. and Brown, M. S. (1997) Differential expression of exon 1a and 1c in mRNAs for sterol element binding protein-1 in human and mouse organs and cultures cells. J. Clin. Invest. 99, 838- 845.

  4. Shimomura, I., Bashmakov, Y., Shimano, H., Horton, J. D., Goldstein, J. L. and Brown, M. S. (1997) Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver. Proc. Natl. Acad. Sci. USA. 94, 12354-12359.

  5. Shimomura, I., Hammer, R. E., Richardson, J. A., Ikemoto, S., Bashmakov, Y., Goldstein, J. L., and M. S. Brown. (1998) Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes & Dev. 12, 3182-3194.

  6. Shimomura, I., Shimano, H., Korn, B., Bashmakov, Y., and J. D. Horton. (1998) Nuclear sterol regulatory element binding proteins activate genes responsible for entire program of unsaturates fatty acid biosynthesis in transgenic mouse liver. J. Biol. Chem. 273, 35299-306.

  7. Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S., and Goldstein, J. L. (1999) Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401(6748), 73-6.

  8. Shimomura, I., Bashmakov, Y., and Horton, J. D. (1999) Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem. 274(42), 30028-32.

  9. Shimomura, I., Bashmakov, Y., Ikemoto, S., Horton, J. D., Brown, M. S., and Goldstein, J. L. (1999) Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. Proc Natl Acad Sci U S A. 96 (24), 13656-13661.

  10. Shimomura, I., Matsuda, M., Hammer, R. E., Bashmakov, Y., Brown, M. S., and Goldstein, J. L. (2000) Down regulation of IRS- 2 and Up-regulation of SREBP-1c leads to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Molecular Cell 6, 77-86.

  11. Matsuda, M., Korn, B.S., Hammer, R.E., Moon, Y-A., Komuro, R., Horton, J.D., Goldstein, J.L., Brown, M.S. and Shimomura, I. (2001) SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. Genes & Dev. 15, 1206-16.

  12. Kishida, K., Shimomura, I. (Corespondent author), Kondo, H., Kuriyama, H., Makino, Y., Nishizawa, H., Maeda, N., Matsuda, M., Kihara, S., Kurachi, Y., Funahashi, T. and Matsuzawa, Y. (2001) Genomic Structure and Insulin-mediated Repression of the Aquaporin Adipose (AQPap), Adipose-specific Glycerol Channel. J Biol Chem. 276, 36251-36260.

  13. Kishida, K., Shimomura, I. (Corespondent author), Nishizawa, H., Maeda, N., Kuriyama, H., Kondo, H., Matsuda, M., Nagaretani, H., Ouchi, N., Hotta, K., Kihara, S., Kadowaki, T., Funahashi, T. and Matsuzawa, Y. (2001) Enhancement of the aquaporin adipose (AQPap) gene expression by a peroxisome proliferator-activated receptor g. J Biol Chem. 276, 48572-48579.

  14. Kondo, H., Shimomura, I. (Corespondent author), Kishida, K., Nishizawa, H., Maeda, N., Kuriyama, H., Matsuda, M., Nagaretani, H., Kihara, S., Funahashi, T., and Matsuzawa, Y. (2002) Human AQPap gene; the genomic structure, promoter analysis and functional mutations. Eur. J. Biol. Chem. 269,1814-1826.

  15. Matsumoto, S., Kishida, K., Shimomura, I. (Corespondent author), Maeda, N., Nagaretani, H., Matsuda, M., Nishizawa, H., Kihara, S., Funahashi, T. and Matsuzawa, Y. (2002) Increased Plasma HB-EGF Associated with Obesity and Coronary Artery Disease. Biochem Biophys Res Commun 292, 781-786.

  16. Kondo, H., Shimomura, I., Matsukawa, Y., Kumada, M., Takahashi, M., Matsuda, M., Kihara, S., Kawamoto, T., Sumitsuji, S., Funahashi, T., and Matsuzawa, Y. (2002) Association of adiponectin mutation with type 2 diabetes mellitus. A candidate gene for the insulin resistance syndrome. Diabetes, in press

  17. Nishizawa, H., Shimomura, I. (Correspondent author), Kishida, K., Maeda, N., Nagaretani, H., Kuriyama, H., Matsuda, M., Kondo, H., Furuyama, N., Kihara, S., Nakamura, T., Tochino, Y., Funahashi, T. and Matsuzawa, Y. (2002) Androgens downregulate plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes, in press.

  18. Maeda, N., Shimomura, I. (correspondent author), Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., Furuyama, N., Kondo, H., Takahashi, M., Arita, Y., Komuro, R., Ouchi, N., Kihara, S., Tochino, Y., Okutomi, K., Horie, K., Takeda, S., Aoyama, T., Funahashi, T. and Matsuzawa, Y. (2002) Diet-induced insulin resistance in mice lacking adiponectin. Nature Medicine, in press.

  19. Makishima, M., Kanatani, Y., Yamamoto-Yamaguchi, Y. and Yoshio Honma, Y. (1996) Enhancement of activity of 1?,25- dihydroxyvitamin D3 for growth inhibition and differentiation induction of human myelomonocytic leukemia cells by tretinoin tocoferil, an ?-tocopherol ester of all-trans retinoic acid. Blood 87, 3384-3394.

  20. Makishima, M., Okabe-Kado, J. and Honma, Y. (1998) Growth inhibition and differentiation induction in human monoblastic leukaemia cells by 1??hydroxyvitamin D derivatives and their enhancement by combination with hydroxyurea. British Journal of Cancer 77, 33-39.

  21. Makishima, M., Umesono, K., Shudo, K., Naoe, T., Kishi, K. and Honma, Y. (1998) Induction of differentiation in acute promyelocytic leukemia cells by 9-cis retinoic acid ?-tocopherol ester (9-cis tretinoin tocoferil). Blood 91, 4715-4726.

  22. Makishima, M., Okamoto, A. Y., Repa, J. J., Tu, H., Learned, R. M., Luk, A., Hull, M. V., Lustig, K. D., Mangelsdorf, D. J. and Shan, B. (1999) Identification of a nuclear receptor for bile acids. Science 284: 1362-1365.

  23. Lu, T. T., Makishima, M., Repa, J. J., Schoonjans, K., Kerr, T. A., Auwerx, J. and Mangelsdorf, D. J. (2000) Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Molecular Cell 6:507-515.

  24. Makishima, M., Lu, T. T., Xie, W., Whitfield, G. K., Domoto, H., Evans, R. M., Haussler, M. R. and Mangelsdorf, D. J. (2002) Vitamin D receptor as an intestinal bile acid sensor. Science 296: 1313-1316.     

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