Centers & Labs

RIKEN Center for Integrative Medical Sciences

Laboratory for Metabolic Homeostasis

Team Leader: Naoto Kubota (M.D., Ph.D)
Naoto  Kubota(M.D., Ph.D)

Type 2 diabetes is a chronic metabolic disorder characterized by hyperglycemia with impaired insulin secretion and insulin resistance. Progression to type 2 diabetes is influenced by genetic and environmental or acquired factors, such as a sedentary lifestyle and dietary habits that promote obesity associating with insulin resistance. This laboratory undertakes research to elucidate the mechanisms involved in development of obesity, insulin resistance, type 2 diabetes and progression of metabolic syndrome, atherosclerosis at the molecular level, and develops innovative diagnosis and treatment methods based on the above findings, which can be applied to the clinical field.

Research Subjects

  • The role of IRS in the regulation of glucose and lipid metabolism in liver
  • The role of IRS in the regulation of glucose in macrophage
  • Elucidation of the mechanism of IRS expression
  • The identification a causative relationship between gut microbes and obesity

Selected Publications

Papers with an asterisk(*) are based on research conducted outside of RIKEN.
  1. Hashimoto, S., Kubota, N., Sato, H., Sasaki, M., Takamoto, I., Kubota, T., Nakaya, K., Noda, M., Ueki, K., Kadowaki, T.:
    "Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion."
    Diabetes 64, 876-86 (2015).
  2. Takamoto, I., Kubota, N., Nakaya, K., Kumagai, K., Hashimoto, S., Kubota, T., Inoue, M., Kajiwara, E., Katsuyama, H., Obata, A., Sakurai, Y., Iwamoto, M., Kitamura, T., Ueki, K., and Kadowaki, T.:
    "TCF7L2 in mouse pancreatic beta cells plays a crucial role in glucose homeostasis by regulating beta cell mass."
    Diabetologia 57, 542-553 (2014).
  3. *Kadowaki, T., Ueki, K., Yamauchi, T., and Kubota, N.:
    "SnapShot: Insulin signaling pathways."
    Cell 148, 624, 624.e1 (2012).
  4. *Kubota T*., Kubota N*#., Kumagai H*., Yamaguchi S., Kozono H., Takahashi T., Inoue M., Itoh S., Takamoto I., Sasako T., Kumagai K., Kawai T., Hashimoto S., Kobayashi T., Sato M., Tokuyama K., Nishimura S., Tsunoda M., Ide T., Murakami K., Yamazaki T., Ezaki O., Kawamura K., Masuda H., Moroi M., Sugi K., Oike Y., Shimokawa H., Yanagihara N., Tsutsui M., Terauchi Y., Tobe K., Nagai R., Kamata K., Inoue K., Kodama T., Ueki K., and Kadowaki T.:
    "Impaired insulin signaling in the endothelial cells reduces insulin-induced glucose uptake by the skeletal muscle. (*co-first authors, #co- corresponding authors)."
    Cell Metabolism 13, 294-307 (2011).
  5. *Kubota N., Kubota T., Itoh S., Kumagai H., Kozono H., Takamoto I., Mineyama T., Ogata H., Tokuyama K., Ohsugi M., Sasako T., Moroi M., Sugi K., Kakuta S., Iwakura Y., Noda T., Ohnishi S., Nagai R., Tobe K., Terauchi Y., Ueki K., and Kadowaki T.:
    "Dynamic functional relay between insulin receptor substrate 1 and 2 in hepatic insulin signaling during fasting and feeding."
    Cell Metabolism 8, 49-64 (2008).
  6. *Kubota N., Yano W., Kubota T., Yamauchi T., Itoh S., Kumagai H., Kozono H., Takamoto I., Okamoto S., Shiuchi T., Suzuki R., Satoh H., Tsuchida A., Moroi M., Sugi K., Noda T., Ebinuma H., Ueta Y., Kondo T., Araki E., Ezaki O., Nagai R., Tobe K., Terauchi Y., Ueki K., Minokoshi Y., and Kadowaki T.:
    "Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake."
    Cell Metabolism 6, 55-68 (2007).
  7. *Kubota N., Terauchi Y., Kubota T., Kumagai H., Itoh S., Satoh H., Yano W., Ogata H., Tokuyama K., Takamoto I., Mineyama T., Ishikawa M., Moroi M., Sugi K., Yamauchi T., Ueki K., Tobe K., Noda T., Nagai R., and Kadowaki T.:
    "Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways."
    J. Biol. Chem. 281, 8748-8755 (2006).
  8. *Kubota N., Terauchi Y., Tobe K., Yano W., Suzuki R., Ueki K., Takamoto I., Satoh H., Maki T., Kubota T., Moroi M., Okada-Iwabu M., Ezaki O., Nagai R., Ueta Y., Kadowaki T., and Noda T.:
    "Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus."
    J. Clin. Invest. 114, 917-927 (2004).
  9. *Kubota N., Terauchi Y., Yamauchi T., Kubota T., Moroi M., Matsui J., Eto K., Yamashita T., Kamon J., Satoh H., Yano W., Froguel P., Nagai R., Kimura S., Kadowaki T., and Noda T.:
    "Disruption of adiponectin causes insulin resistance and neointimal formation."
    J. Biol. Chem. 277, 25863-25866 (2002).
  10. *Kubota N., Tobe K., Terauchi Y., Eto K., Yamauchi T., Suzuki R., Tsubamoto Y., Komeda K., Nakano R., Miki H., Satoh S., Sekihara H., Sciacchitano S., Lesniak M., Aizawa S., Nagai R., Kimura S., Akanuma Y., Taylor SI., and Kadowaki T.:
    "Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory beta-cell hyperplasia."
    Diabetes 49, 1880-1889 (2000).

Lab Members

Principal Investigator

Naoto Kubota
Team Leader

Core Members

Tetsuya Kubota
Senior Research Scientist
Miki Igarashi
Research Scientist

Contact information

1-7-22 Suehiro-cho, Tsurumi-ku,
Yokohama City, Kanagawa,
230-0045, Japan
Tel: +81-(0)45-503-9111 (Ext: #6483)

Email: naoto.kubota [at]

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