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Publication : Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin.

First Author  Wang Q Year  2014
Journal  Mol Metab Volume  3
Issue  1 Pages  64-72
PubMed ID  24567905 Mgi Jnum  J:221292
Mgi Id  MGI:5638838 Doi  10.1016/j.molmet.2013.10.001
Citation  Wang Q, et al. (2014) Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin. Mol Metab 3(1):64-72
abstractText  The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreER(T2) transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia.
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