| First Author | Sabatini PV | Year | 2018 |
| Journal | Cell Rep | Volume | 22 |
| Issue | 1 | Pages | 163-174 |
| PubMed ID | 29298418 | Mgi Jnum | J:270781 |
| Mgi Id | MGI:6278714 | Doi | 10.1016/j.celrep.2017.12.033 |
| Citation | Sabatini PV, et al. (2018) Neuronal PAS Domain Protein 4 Suppression of Oxygen Sensing Optimizes Metabolism during Excitation of Neuroendocrine Cells. Cell Rep 22(1):163-174 |
| abstractText | Depolarization of neuroendocrine cells results in calcium influx, which induces vesicle exocytosis and alters gene expression. These processes, along with the restoration of resting membrane potential, are energy intensive. We hypothesized that cellular mechanisms exist to maximize energy production during excitation. Here, we demonstrate that NPAS4, an immediate early basic helix-loop-helix (bHLH)-PAS transcription factor, acts to maximize energy production by suppressing hypoxia-inducible factor 1alpha (HIF1alpha). As such, knockout of Npas4 from insulin-producing beta cells results in reduced OXPHOS, loss of insulin secretion, beta cell dedifferentiation, and type 2 diabetes. NPAS4 plays a similar role in the nutrient-sensing cells of the hypothalamus. Its knockout here results in increased food intake, reduced locomotor activity, and elevated peripheral glucose production. In conclusion, NPAS4 is critical for the coordination of metabolism during the stimulation of electrically excitable cells; its loss leads to the defects in cellular metabolism that underlie the cellular dysfunction that occurs in metabolic disease. |
