Abstract

Objective: 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 MCR in individual medial hypothalamic nuclei to regulation of peripheral glucose uptake have remained unclear. We examined the effects of injection of leptin and the MCR agonist MT-II into medial hypothalamic nuclei on glucose uptake in peripheral tissues.

Research Design and Methods: Leptin or MT-II was injected into the ventromedial (VMH), dorsomedial (DMH), arcuate (ARC), or paraventricular (PVH) hypothalamus or the lateral ventricle (i.c.v.) in freely moving mice. The MCR antagonist SHU9119 was injected i.c.v. Glucose uptake was measured by the 2-[³H]deoxy-D-glucose method.

Results: Leptin injection into VMH increased glucose uptake in skeletal muscle, brown adipose tissue (BAT), and heart, whereas that into ARC increased glucose uptake in BAT and that into DMH or PVH had no effect. SHU9119 abolished these effects of leptin injected into VMH. Injection of MT-II either into VMH or i.c.v. increased glucose uptake in skeletal muscle, BAT, and heart, whereas that into PVH increased glucose uptake in BAT and that into DMH or ARC had no effect.

Conclusions: 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 ARC and MCR in PVH regulate glucose uptake in BAT. Medial hypothalamic nuclei thus play distinct roles in leptin- and MT-II-induced glucose uptake in peripheral tissues.