Release of insulin produced by the choroid plexis is regulated by serotonergic signaling
| Autor: | Jennifer F. O’Connell, Josephine M. Egan, Nicholas S. Huang, Simonetta Camandola, Qing-Rong Liu, Caio Henrique Mazucanti, Doyle Lu Lang |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Serotonin medicine.medical_specialty medicine.medical_treatment Gene Expression Serotonergic Mice 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid Dorsal raphe nucleus Neurotrophic factors Internal medicine medicine Animals Humans Insulin RNA Messenger Receptor Cerebrospinal Fluid Chemistry Brain Epithelial Cells General Medicine Mice Inbred C57BL Molecular Docking Simulation Glucose 030104 developmental biology Endocrinology Blood-Brain Barrier 030220 oncology & carcinogenesis Choroid Plexus Calcium Choroid plexus Research Article Signal Transduction |
| Zdroj: | JCI Insight. 4 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.131682 |
| Popis: | The choroid plexus (ChP) is a highly vascularized tissue found in the brain ventricles, with an apical epithelial cell layer surrounding fenestrated capillaries. It is responsible for the production of most of the cerebrospinal fluid (CSF) in the ventricular system, subarachnoid space, and central canal of the spinal cord, while also constituting the blood-CSF barrier (BCSFB). In addition, epithelial cells of the ChP (EChP) synthesize neurotrophic factors and other signaling molecules that are released into the CSF. Here, we show that insulin is produced in EChP of mice and humans, and its expression and release are regulated by serotonin. Insulin mRNA and immune-reactive protein, including C-peptide, are present in EChP, as detected by several experimental approaches, and appear in much higher levels than any other brain region. Moreover, insulin is produced in primary cultured mouse EChP, and its release, albeit Ca(2+) sensitive, is not regulated by glucose. Instead, activation of the 5HT2C receptor by serotonin treatment led to activation of IP3-sensitive channels and Ca(2+) mobilization from intracellular storage, leading to insulin secretion. In vivo depletion of brain serotonin in the dorsal raphe nucleus negatively affected insulin expression in the ChP, suggesting an endogenous modulation of ChP insulin by serotonin. Here, we show for the first time to our knowledge that insulin is produced by EChP in the brain, and its release is modulated at least by serotonin but not glucose. |
| Databáze: | OpenAIRE |
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