@article{7a0fb7edfd0f4d01a368f1998196e89f,
title = "Hypothalamic Orexin Stimulates Feeding-Associated Glucose Utilization in Skeletal Muscle via Sympathetic Nervous System",
abstract = "Hypothalamic neurons containing orexin (hypocretin) are activated during motivated behaviors and active waking. We show that injection of orexin-A into the ventromedial hypothalamus (VMH) of mice or rats increased glucose uptake and promoted insulin-induced glucose uptake and glycogen synthesis in skeletal muscle, but not in white adipose tissue, by activating the sympathetic nervous system. These effects of orexin were blunted in mice lacking β-adrenergic receptors but were restored by forced expression of the β2-adrenergic receptor in both myocytes and nonmyocyte cells of skeletal muscle. Orexin neurons are activated by conditioned sweet tasting and directly excite VMH neurons, thereby increasing muscle glucose metabolism and its insulin sensitivity. Orexin and its receptor in VMH thus play a key role in the regulation of muscle glucose metabolism associated with highly motivated behavior by activating muscle sympathetic nerves and β2-adrenergic signaling.",
keywords = "HUMDISEASE",
author = "Tetsuya Shiuchi and Haque, {Mohammad Shahidul} and Shiki Okamoto and Tsuyoshi Inoue and Haruaki Kageyama and Suni Lee and Chitoku Toda and Atsushi Suzuki and Bachman, {Eric S.} and Kim, {Young Bum} and Takashi Sakurai and Masashi Yanagisawa and Seiji Shioda and Keiji Imoto and Yasuhiko Minokoshi",
note = "Funding Information: We thank B.B. Lowell for providing β-less mice, K. Morohashi for providing antibodies to SF1, O. Ezaki for providing the HSA gene promoter, M. Morimatsu for providing the CAG promoter, K. Saito for breeding β-less mice, the Center for Analytical Instruments at the National Institute for Basic Biology (NIBB, Okazaki, Japan) for DNA sequencing, and the Center for Radioisotope Facilities at the NIBB for measurement of in vivo glucose metabolism and enzyme activity. This work was supported by a Grant-in-Aid for Scientific Research (B) (19390059 and 21390067, to Y.M.), a Grant-in-Aid for Young Scientists (B) (17790634 and 19790653, to T.S.), and a Grant-in-Aid for Scientific Research on Priority Areas (19045029, Cell Sensor, to Y.M.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan as well as by The Specific Research Fund of the National Institutes for Natural Sciences and the Research Program of Hayama Center for Advanced Studies of Sokendai (to Y.M.). ",
year = "2009",
month = dec,
day = "2",
doi = "10.1016/j.cmet.2009.09.013",
language = "English (US)",
volume = "10",
pages = "466--480",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "6",
}