近日，中科院上海生科院营养所研究员郭非凡小组发现催乳素受体调节胰岛素敏感性的新功能，并首次证实了催乳素受体在调节肝脏胰岛素敏感性方面的重要作用，提示催乳素受体可能是一种预防和治疗糖尿病的潜在药物分子靶标。相关研究成果在线发表在新一期的《糖尿病》上。
研究表明，激素与胰岛素敏感性调节密切相关，特别是催乳素作为一种主要由垂体分泌的激素，与胰岛素敏感性的关系近来备受关注。但是，其调控作用却存在很大争议，且其作用机制有待于深入研究。
在郭非凡的指导下，研究生于俊杰、肖斐等通过从“介导催乳素作用的催乳素受体（PRLR）”入手，对PRLR调节胰岛素敏感性的作用和机制进行了全面系统的研究，揭示了PRLR通过激活STAT5来调节胰岛素敏感性的生理机制。研究发现在小鼠通过腺病毒过度表达PRLR能增强肝脏胰岛素敏感性，而敲低PRLR表达则降低肝脏胰岛素敏感性；另外，利用胰岛素抵抗的db/db小鼠模型和亮氨酸缺乏饮食诱导的胰岛素敏感性增强小鼠模型，进一步证实了催乳素受体对胰岛素敏感性的调节作用。（生物谷 Bioon.com）
生物谷推荐的英文摘要
Diabetes doi: 10.2337/db13-0182
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
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.
