Imperial College London
Professor Dominic Withers

ProfessorDominicWithers

Faculty of Medicine, Institute of Clinical Sciences

Clinical Chair in Diabetes & Endocrinology
 
 
 
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Contact

 

d.withers

 
 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Smith:2018:10.1016/j.celrep.2018.09.024,
author = {Smith, MA and Katsouri, L and Virtue, S and Choudhury, A and Vidal-Puig, A and Ashford, MLJ and Withers, DJ},
doi = {10.1016/j.celrep.2018.09.024},
journal = {Cell Reports},
pages = {278--287},
title = {Calcium channel CaV2.3 subunits regulate hepatic glucose production by modulating leptin-induced excitation of arcuate pro-opiomelanocortin neurons},
url = {http://dx.doi.org/10.1016/j.celrep.2018.09.024},
volume = {25},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Smith,MA
AU  - Katsouri,L
AU  - Virtue,S
AU  - Choudhury,A
AU  - Vidal-Puig,A
AU  - Ashford,MLJ
AU  - Withers,DJ
DO  - 10.1016/j.celrep.2018.09.024
EP  - 287
PY  - 2018///
SN  - 2211-1247
SP  - 278
TI  - Calcium channel CaV2.3 subunits regulate hepatic glucose production by modulating leptin-induced excitation of arcuate pro-opiomelanocortin neurons
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2018.09.024
UR  - http://hdl.handle.net/10044/1/63166
VL  - 25
ER  -
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