| First Author | Smith MA | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 2 | Pages | 278-287.e4 |
| PubMed ID | 30304668 | Mgi Jnum | J:270836 |
| Mgi Id | MGI:6278324 | Doi | 10.1016/j.celrep.2018.09.024 |
| Citation | Smith MA, et al. (2018) Calcium Channel CaV2.3 Subunits Regulate Hepatic Glucose Production by Modulating Leptin-Induced Excitation of Arcuate Pro-opiomelanocortin Neurons. Cell Rep 25(2):278-287.e4 |
| abstractText | 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. |
