近日，中科院上海生科院營養(yǎng)所研究員郭非凡小組發(fā)現(xiàn)催乳素受體調(diào)節(jié)胰島素敏感性的新功能,，并首次證實(shí)了催乳素受體在調(diào)節(jié)肝臟胰島素敏感性方面的重要作用,，提示催乳素受體可能是一種預(yù)防和治療糖尿病的潛在藥物分子靶標(biāo),。相關(guān)研究成果在線發(fā)表在新一期的《糖尿病》上,。
研究表明，激素與胰島素敏感性調(diào)節(jié)密切相關(guān),，特別是催乳素作為一種主要由垂體分泌的激素，與胰島素敏感性的關(guān)系近來備受關(guān)注,。但是，其調(diào)控作用卻存在很大爭(zhēng)議,，且其作用機(jī)制有待于深入研究,。
在郭非凡的指導(dǎo)下，研究生于俊杰,、肖斐等通過從“介導(dǎo)催乳素作用的催乳素受體（PRLR）”入手,，對(duì)PRLR調(diào)節(jié)胰島素敏感性的作用和機(jī)制進(jìn)行了全面系統(tǒng)的研究，揭示了PRLR通過激活STAT5來調(diào)節(jié)胰島素敏感性的生理機(jī)制,。研究發(fā)現(xiàn)在小鼠通過腺病毒過度表達(dá)PRLR能增強(qiáng)肝臟胰島素敏感性,，而敲低PRLR表達(dá)則降低肝臟胰島素敏感性；另外,，利用胰島素抵抗的db/db小鼠模型和亮氨酸缺乏飲食誘導(dǎo)的胰島素敏感性增強(qiáng)小鼠模型,，進(jìn)一步證實(shí)了催乳素受體對(duì)胰島素敏感性的調(diào)節(jié)作用,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
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.
