Central prolactin receptors (PRLRs) regulate hepatic insulin sensitivity in mice via signal transducer and activator of transcription 5 (STAT5) and the vagus nerve
| Autor: | Chunxia Wang, Yuzhong Xiao, Shanghai（陈上海） Chen, Yajie Guo, Fei Xiao, Ziquan Lv, Kai Li, Qian Zhang, Hao Liu, Bin Liu, Junjie Yu, Tingting Xia, Jiali Deng, Feifan（郭非凡） Guo |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Receptors Prolactin Endocrinology Diabetes and Metabolism Hypothalamus Biology Real-Time Polymerase Chain Reaction Mice Insulin resistance Internal medicine STAT5 Transcription Factor Internal Medicine medicine Animals Receptor Cells Cultured STAT5 Neurons Prolactin receptor Vagus Nerve medicine.disease Prolactin Vagus nerve Mice Inbred C57BL Endocrinology Liver STAT protein biology.protein Insulin Resistance |
| Zdroj: | Diabetologia. 57:2136-2144 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-014-3336-3 |
| Popis: | Recent studies have revealed the crucial role of the central nervous system (CNS), especially the hypothalamus, in the regulation of insulin sensitivity in peripheral tissues. The aim of our current study was to investigate the possible involvement of hypothalamic prolactin receptors (PRLRs) in the regulation of hepatic insulin sensitivity. We employed overexpression of PRLRs in mouse hypothalamus via intracerebroventricular injection of adenovirus expressing PRLR and inhibition of PRLRs via adenovirus expressing short-hairpin RNA (shRNA) specific for PRLRs in vivo. Selective hepatic vagotomy was employed to verify the important role of the vagus nerve in mediating signals from the brain to peripheral organs. In addition, a genetic insulin-resistant animal model, the db/db mouse, was used in our study to investigate the role of hypothalamic PRLRs in regulating whole-body insulin sensitivity. Overexpression of PRLRs in the hypothalamus improved hepatic insulin sensitivity in mice and inhibition of hypothalamic PRLRs had the opposite effect. In addition, we demonstrated that hypothalamic PRLR-improved insulin sensitivity was significantly attenuated by inhibiting the activity of signal transducer and activator of transcription 5 (STAT5) in the CNS and by selective hepatic vagotomy. Finally, overexpression of PRLRs significantly ameliorated insulin resistance in db/db mice. Our study identifies a novel central pathway involved in the regulation of hepatic insulin sensitivity, mediated by hypothalamic PRLR/STAT5 signalling and the vagus nerve, thus demonstrating an important role for hypothalamic PRLRs under conditions of insulin resistance. |
| Databáze: | OpenAIRE |
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