Prolactin Receptor (PRLR) regulates hepatic insulin sensitivity in mice via Signal Transducer and Activator of Transcription (STAT)5
- Junjie Yu#,
- Fei Xiao#,
- Qian Zhang,
- Bin Liu,
- Yajie Guo,
- Ziquan Lv,
- Tingting Xia,
- Shanghai Chen,
- Kai Li,
- Ying Du and
- Feifan Guo*
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences 294 Taiyuan Road, Shanghai, China 200031
- *Corresponding Author: Feifan Guo
# Junjie Yu and Fei Xiao contributed equally to this study
Insulin resistance is one of the major contributing factors in the development of metabolic diseases. The mechanisms responsible for insulin resistance, however, remain poorly understood. Although numerous functions of the prolactin receptor (PRLR) have been identified, a direct effect on insulin sensitivity has not been previously described. The aim of our current study is to investigate this possibility and elucidate underlying mechanisms. Here we show that insulin sensitivity is improved or impaired in mice injected with adenovirus that over-express or knock down PRLR expression, respectively. Similar observations were obtained in in vitro studies. In addition, we discovered that the Signal Transducer and Activator of Transcription (STAT)5 pathway is required for regulating insulin sensitivity by PRLR. Moreover, we observed that PRLR expression is decreased or increased under insulin-resistant (db/db) or insulin-sensitive (leucine deprivation) conditions, respectively, and found that altering PRLR expression significantly reverses insulin sensitivity under both conditions. Finally, we found that PRLR expression levels are increased under leucine deprivation via a General Control Nonderepressible (GCN)2/mammalian Target of Rapamycin (mTOR)/ribosomal protein S6 Kinase-1 (S6K1)-dependent pathway. These results demonstrate a novel function for hepatic PRLR in the regulation of insulin sensitivity and provide important insights concerning the nutritional regulation of PRLR expression.
- Received February 1, 2013.
- Accepted June 10, 2013.
- © 2013 by the American Diabetes Association.
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