PT  - JOURNAL ARTICLE
AU  - Ikuko Sato
AU  - Hiroshi Arima
AU  - Noriyuki Ozaki
AU  - Minemori Watanabe
AU  - Motomitsu Goto
AU  - Masayuki Hayashi
AU  - Ryouichi Banno
AU  - Hiroshi Nagasaki
AU  - Yutaka Oiso
TI  - Insulin Inhibits Neuropeptide Y Gene Expression in the Arcuate Nucleus through GABAergic Systems
AID  - 10.1523/JNEUROSCI.2739-05.2005
DP  - 2005 Sep 21
TA  - The Journal of Neuroscience
PG  - 8657--8664
VI  - 25
IP  - 38
4099  - http://www.jneurosci.org/content/25/38/8657.short
4100  - http://www.jneurosci.org/content/25/38/8657.full
SO  - J. Neurosci.2005 Sep 21; 25
AB  - Neuropeptide Y (NPY) in the arcuate nucleus is an orexigenic hormone of which levels are regulated by humoral as well as neural signals. In this study, we examined the regulation of NPY gene expression in the arcuate nucleus in hypothalamic organotypic cultures. Dexamethasone (DEX) (10–9 to 10–7 m) significantly increased NPY mRNA expression, and the effects were not influenced by coincubation with the sodium channel blocker tetrodotoxin (TTX), indicating that the action of DEX is independent of action potentials. Conversely, insulin (10–11 to 10–9 m) significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was abolished in the presence of TTX. Because GABA and its receptors are expressed in the arcuate nucleus in vivo, we examined whether GABAergic systems were involved in the insulin action. The GABAB agonist baclofen significantly inhibited NPY expression stimulated by DEX, and the inhibitory action of insulin was completely abolished in the presence of either the GABAA antagonist bicuculline or the GABAB antagonist CGP35348 (p-3-aminopropyl-p-diethoxymethyl phosphoric acid). Furthermore, increases in the GABA-synthesizing enzyme glutamic acid decarboxylase 65 (GAD65) mRNA expression preceded decreases in NPY mRNA expression in the arcuate nucleus in the cultures. Experiments in vivo also demonstrated that increases in GAD65 mRNA expression in the arcuate nucleus preceded decreases in the NPY mRNA expression in a fasting-refeeding paradigm and that intracerebroventricular injection of insulin increased GAD65 mRNA expression in the arcuate nucleus in fasted rats. These data suggest that insulin inhibits NPY gene expression in the arcuate nucleus through GABAergic systems.