Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system.
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 beta-adrenergic receptors but were restored by forced expression of the beta(2)-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 beta(2)-adrenergic signaling.
Shiuchi
Tetsuya
T
Division of Endocrinology and Metabolism, Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Haque
Mohammad Shahidul
MS
Okamoto
Shiki
S
Inoue
Tsuyoshi
T
Kageyama
Haruaki
H
Lee
Suni
S
Toda
Chitoku
C
Suzuki
Atsushi
A
Bachman
Eric S
ES
Kim
Young-Bum
YB
Sakurai
Takashi
T
Yanagisawa
Masashi
M
Shioda
Seiji
S
Imoto
Keiji
K
Minokoshi
Yasuhiko
Y
D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D005247:Feeding Behavior / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009042:Motivation / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism; D013566:Sympathomimetics / Q000378:metabolism / Q000494:pharmacology; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*
D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D011943:Receptors, Adrenergic, beta; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D013566:Sympathomimetics; D006003:Glycogen; D005947:Glucose