Distinct effects of leptin and a melanocortin receptor agonist injected into medial hypothalamic nuclei on glucose uptake in peripheral tissues.
Distinct effects of leptin and a melanocortin receptor agonist injected into medial hypothalamic nuclei on glucose uptake in peripheral tissues.
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DOI：
10.2337/db09-0638
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发表时间：
2009-12
期刊：
影响因子：
7.7
通讯作者：
Minokoshi Y
中科院分区：
文献类型：
--
作者：
Toda C;Shiuchi T;Lee S;Yamato-Esaki M;Fujino Y;Suzuki A;Okamoto S;Minokoshi Y
下丘脑内侧介导瘦素诱导的外周组织葡萄糖摄取，脑黑素皮质素受体（mcr）介导瘦素的某些中枢作用。然而，个体下丘脑内侧核的瘦素受体和mcr对外周葡萄糖摄取调节的作用仍不清楚。我们研究了在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注射到自由运动小鼠的腹内侧（VMH）、背内侧（DMH）、弓形核（ARC）或室旁（PVH）下丘脑或侧脑室（脑室内）。脑室内注射MCR拮抗剂SHU9119。葡萄糖摄取用2-[3H]脱氧-d-葡萄糖法测定。瘦素注射到VMH增加了骨骼肌、棕色脂肪组织（BAT）和心脏的葡萄糖摄取，而注射到ARC增加了BAT的葡萄糖摄取，注射到DMH或PVH没有影响。SHU9119消除了瘦素注射到VMH的这些作用。在VMH或脑室内注射MT-II增加了骨骼肌、BAT和心脏的葡萄糖摄取，而在PVH注射MT-II增加了BAT的葡萄糖摄取，在DMH或ARC注射MT-II没有影响。VMH介导骨骼肌、BAT和心脏中瘦素和mt - ii诱导的葡萄糖摄取。瘦素的这些作用依赖于MCR的激活。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起着不同的作用。
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-[3H]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.