title: PRLR regulates hepatic insulin sensitivity in mice via STAT5.
abstract: 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 overexpress 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-5 pathway are required for regulating insulin sensitivity by PRLR. Moreover, we observed that PRLR expression is decreased or increased under insulin-resistant (db/db mice) 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 2/mammalian target of rapamycin/ribosomal protein S6 kinase-1-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.
authors.affiliation: 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, Shanghai, People's Republic of China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yu
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Yajie
authors.initials: Y
authors.lastname: Guo
authors.forename: Ziquan
authors.initials: Z
authors.lastname: Lv
authors.forename: Tingting
authors.initials: T
authors.lastname: Xia
authors.forename: Shanghai
authors.initials: S
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.forename: Feifan
authors.initials: F
authors.lastname: Guo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; C070634:Eif2ak4 protein, mouse; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa