Distinct effects of leptin and a melanocortin receptor agonist injected into medial hypothalamic nuclei on glucose uptake in peripheral tissues.
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 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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Toda
Chitoku
C
Department of Physiological Sciences, Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa, Japan.
Shiuchi
Tetsuya
T
Lee
Suni
S
Yamato-Esaki
Maya
M
Fujino
Yusuke
Y
Suzuki
Atsushi
A
Okamoto
Shiki
S
Minokoshi
Yasuhiko
Y
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002552:Cerebral Ventricles; D005947:Glucose / Q000378:metabolism*; D007033:Hypothalamus, Middle; D015151:Immunoblotting; D007267:Injections; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000378:metabolism*; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014316:Tritium; D014697:Ventromedial Hypothalamic Nucleus; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism
D020738:Leptin; D010456:Peptides, Cyclic; D044101:Receptors, Melanocortin; D014316:Tritium; C079282:melanotan-II; C103272:SHU 9119; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones; D005947:Glucose