Toda Chitoku, Shiuchi Tetsuya, Lee Suni, Yamato-Esaki Maya, Fujino Yusuke, Suzuki Atsushi, Okamoto Shiki, Minokoshi Yasuhiko
Department of Physiological Sciences, Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa, Japan.
Diabetes. 2009 Dec;58(12):2757-65. doi: 10.2337/db09-0638. Epub 2009 Sep 14.
The medial hypothalamus mediates leptin-induced glucose uptake in peripheral tissues, and brain melanocortin receptors (MCRs) mediate certain central effects of leptin. However, the contributions of the leptin receptor and MCRs in individual medial hypothalamic nuclei to regulation of peripheral glucose uptake have remained unclear. We examined the effects of an injection of leptin and the MCR agonist MT-II into medial hypothalamic nuclei on glucose uptake in peripheral tissues.
Leptin or MT-II was injected into the ventromedial (VMH), dorsomedial (DMH), arcuate nucleus (ARC), or paraventricular (PVH) hypothalamus or the lateral ventricle (intracerebroventricularly) in freely moving mice. The MCR antagonist SHU9119 was injected intracerebroventricularly. Glucose uptake was measured by the 2-[(3)H]deoxy-d-glucose method.
Leptin injection into the VMH increased glucose uptake in skeletal muscle, brown adipose tissue (BAT), and heart, whereas that into the ARC increased glucose uptake in BAT, and that into the DMH or PVH had no effect. SHU9119 abolished these effects of leptin injected into the VMH. Injection of MT-II either into the VMH or intracerebroventricularly increased glucose uptake in skeletal muscle, BAT, and heart, whereas that into the PVH increased glucose uptake in BAT, and that into the DMH or ARC had no effect.
The VMH mediates leptin- and MT-II-induced glucose uptake in skeletal muscle, BAT, and heart. These effects of leptin are dependent on MCR activation. The leptin receptor in the ARC and MCR in the PVH regulate glucose uptake in BAT. Medial hypothalamic nuclei thus play distinct roles in leptin- and MT-II-induced glucose uptake in peripheral tissues.
下丘脑内侧介导瘦素诱导的外周组织葡萄糖摄取，而脑黑皮质素受体（MCRs）介导瘦素的某些中枢效应。然而，瘦素受体和MCRs在单个下丘脑内侧核中对外周葡萄糖摄取调节的作用仍不清楚。我们研究了向小鼠下丘脑内侧核注射瘦素和MCR激动剂MT-II对外周组织葡萄糖摄取的影响。
将瘦素或MT-II注射到自由活动小鼠的腹内侧（VMH）、背内侧（DMH）、弓状核（ARC）、室旁（PVH）下丘脑或侧脑室（脑室内）。脑室内注射MCR拮抗剂SHU9119。采用2-[(3)H]脱氧-D-葡萄糖法测量葡萄糖摄取。
向VMH注射瘦素可增加骨骼肌、棕色脂肪组织（BAT）和心脏的葡萄糖摄取，而向ARC注射瘦素可增加BAT的葡萄糖摄取，向DMH或PVH注射则无影响。SHU9119消除了向VMH注射瘦素的这些效应。向VMH或脑室内注射MT-II可增加骨骼肌、BAT和心脏的葡萄糖摄取，而向PVH注射可增加BAT的葡萄糖摄取，向DMH或ARC注射则无影响。
VMH介导瘦素和MT-II诱导的骨骼肌、BAT和心脏的葡萄糖摄取。瘦素的这些效应依赖于MCR激活。ARC中的瘦素受体和PVH中的MCR调节BAT中的葡萄糖摄取。因此，下丘脑内侧核在瘦素和MT-II诱导的外周组织葡萄糖摄取中发挥不同作用。
