Laboratory for Metabolic Homeostasis

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 Fields

Molecular Biology & Genetics / Clinical Medicine

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

Publications

1. Kubota N., Terauchi Y., Miki H., Tamemoto H., Yamauchi T., Komeda K., Satoh S., Nakano R., Ishii C., Sugiyama T., Eto K., Tsubamoto Y., Okuno A., Murakami K., Sekihara H., Hasegawa G., Naito M., Toyoshima Y., Tanaka S., Shiota K., Kitamura T., Fujita T., Ezaki O., Aizawa S., Kadowaki T., et al.:
   "PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance."
   Molecular Cell 4: 597-609, 1999.
2. Eto K., Tsubamoto Y., Terauchi Y., Sugiyama T., Kishimoto T., Takahashi N., Yamauchi N., Kubota N., Murayama S., Aizawa T., Akanuma Y., Aizawa S., Kasai H., Yazaki Y., Kadowaki T.:
   "Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion."
   Science 283: 981-985, 1999.
3. 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., 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.
4. Yamauchi T., Kamon J., Waki H., Terauchi Y., Kubota N., Hara K., Mori Y., Ide T., Murakami K., Tsuboyama-Kasaoka N., Ezaki O., Akanuma Y., Gavrilova O., Vinson C., Reitman M.L., Kagechika H., Shudo K., Yoda M., Nakano Y., Tobe K., Nagai R., Kimura S., Tomita M., Froguel P., Kadowaki T.:
   "The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity."
   Nature Medicine 7: 941-946, 2001.
5. 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., Noda T.:
   "Disruption of adiponectin causes insulin resistance and neointimal formation."
   J. Biol. Chem. 277: 25863-25866, 2002.
6. 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., Noda T.:
   "Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus."
   J. Clin. Invest. 114: 917-927, 2004.
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., 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., 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., Kadowaki T.:
   "Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake."
   Cell Metabolism 6: 55-68, 2007.
9. 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., 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.
10. 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., 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