Laboratory of Homeostatic Integration


Associate Professor Nobuaki OKUMURA


Tel 81-6-6879-4312
Fax 81-6-6879-4312


Living organisms have to adopt environmental conditions that are fluctuating hour by hour and day by day. A key environmental factor for an organism is the day/night cycle. In mammals, the hypothalamus produces 24h rhythms of physiology and behavior and organizes homeostatic regulation of blood glucose, energy expenditure, etc. through the autonomic and the endocrine systems. We are studying how the central circadian clock works and how the hypothalamus organizes the homeostatic regulation.

Fig. 1: Homeostatic regulation by the hypothalamus. Homeostasis of internal body conditions such as blood glucose, body temperature, and energy expenditure are regulated by the autonomic nervous system and the endocrine systems under the control of the hypothalamus.
Fig. 2: Localization of carnosinase CN2 in the hypothalamus.We have found that a dipeptide L-carnosine reduces blood glucose and sympathetic nerve activity. More recently, a carnosine-degrading enzyme, CN2, was cloned and was found to be localized in histaminergic neurons of the hypothalamic tuberomammillary nucleus.


Current Research Programs

1. Molecular mechanisms of peptide metabolism

2. Physiological functions of dipeptides

3. Development and application of proteomic techniques


1. Evidence for an essential role of intradimer interaction in catalytic function of carnosine dipeptidase II using electrospray-ionization mass spectrometry.Okumura N et al. (2016) Protein Sci., 25, 511-22.

2. Phospholipid methylation controls Atg32-mediated mitophagy and Atg8 recycling. Sakakibara K  et al. (2015) EMBO J., 342703-19 .

3. Diversity in protein profiles of individual calcium oxalate kidney stones.Okumura N et al. PLoS One., (2013) Jul 9;8(7):e68624 .

4. Identification of cargo proteins specific for importin-β with importin-α applying a stable isotope labeling by amino acids in cell culture (SILAC)-based in vitro transport system. Kimura M et al.(2013) J Biol Chem., 288, 24540-9.

5. Identification of cargo proteins specific for the nucleocytoplasmic transport carrier transportin by combination of an in vitro transport system and stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics. Kimura M et al. (2013) Mol Cell Proteomics., 12, 145-57.

6. Localization of phospho-tyrosine489-β-adducin-immunoreactivity in the hypothalamic tanycytes and its involvement in energy homeostasis. Gotoh, H. et al. (2008) Brain Res., 1228, 97-196.

7. Structural basis for substrate recognition and hydrolysis by mouse carnosinase CN2. Unno H et al. (2008) J. Biol. Chem., 283, 27289-99.

8. Effects of central injection of L-carnosine on sympathetic nerve activity innervating brown adipose tissue and body temperature in rats. Tanida M et al. (2007) Regul Pept., 144, 62-71.