Calcium Channel CaV2.3 Subunits Regulate Hepatic Glucose Production by Modulating Leptin-Induced Excitation of Arcuate Pro-opiomelanocortin Neurons | Zendy

Mark A. Smith | Zendy; Loukia Katsouri | Zendy; Sam Virtue | Zendy; Agharul I. Choudhury | Zendy; António Vidal-Puig | Zendy; Michael L.J. Ashford | Zendy; Dominic J. Withers | Zendy

Open Access

Calcium Channel CaV2.3 Subunits Regulate Hepatic Glucose Production by Modulating Leptin-Induced Excitation of Arcuate Pro-opiomelanocortin Neurons

Author(s) -

Mark A. Smith,

Loukia Katsouri,

Sam Virtue,

Agharul I. Choudhury,

António Vidal-Puig,

Michael L.J. Ashford,

Dominic J. Withers

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.09.024

Subject(s) - leptin , endocrinology , medicine , depolarization , gene knockdown , glucose homeostasis , homeostasis , insulin resistance , calcium channel , arcuate nucleus , chemistry , insulin , hypothalamus , biology , calcium , obesity , biochemistry , gene

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 (Ca V ) conductance with the properties of the "R-type" channel. Knockdown of the pore-forming subunit of the R-type (Ca V 2.3 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.

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