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Calcium channel CaV2.3 subunits regulate hepatic glucose production by modulating leptin-induced excitation of arcuate pro-opiomelanocortin neurons

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Title: Calcium channel CaV2.3 subunits regulate hepatic glucose production by modulating leptin-induced excitation of arcuate pro-opiomelanocortin neurons
Authors: Smith, MA
Katsouri, L
Virtue, S
Choudhury, A
Vidal-Puig, A
Ashford, MLJ
Withers, DJ
Item Type: Journal Article
Abstract: Leptin acts on hypothalamic pro-opiomelanocortin (POMC) neurons to regulate glucose homeostasis, but the precise mechanisms remain unclear. Here, we demonstrate that leptin-induced depolarization of POMC neurons is associated with the augmentation of a voltage-gated calcium (CaV) conductance with the properties of the “R-type” channel. Knockdown of the pore-forming subunit of the R-type (CaV2.3 or Cacna1e) conductance in hypothalamic POMC neurons prevented sustained leptin-induced depolarization. In vivo POMC-specific Cacna1e knockdown increased hepatic glucose production and insulin resistance, while body weight, feeding, or leptin-induced suppression of food intake were not changed. These findings link Cacna1e function to leptin-mediated POMC neuron excitability and glucose homeostasis and may provide a target for the treatment of diabetes.
Issue Date: 9-Oct-2018
Date of Acceptance: 7-Sep-2018
URI: http://hdl.handle.net/10044/1/63166
DOI: https://dx.doi.org/10.1016/j.celrep.2018.09.024
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 278
End Page: 287
Journal / Book Title: Cell Reports
Volume: 25
Issue: 2
Copyright Statement: © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Wellcome Trust
Medical Research Council
Funder's Grant Number: 511377
MC-A654-5QB40
Publication Status: Published
Online Publication Date: 2018-10-09
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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