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PRLR regulates hepatic insulin sensitivity in mice via STAT5

Junjie Yu1, Fei Xiao, Qian Zhang

  • 1Key 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.

Diabetes
|June 19, 2013
PubMed

Insights

This study reveals that the prolactin receptor (PRLR) plays a crucial role in regulating insulin sensitivity. Modulating PRLR levels impacts metabolic health, offering new insights into insulin resistance mechanisms.

Area of Science:

  • Metabolic disease research
  • Endocrinology
  • Molecular biology

Background:

  • Insulin resistance is a key factor in metabolic diseases, but its mechanisms are not fully understood.
  • The prolactin receptor (PRLR) has known functions, but its direct impact on insulin sensitivity was unexplored.

Purpose of the Study:

  • To investigate the role of the prolactin receptor (PRLR) in regulating insulin sensitivity.
  • To elucidate the molecular mechanisms underlying PRLR's effect on insulin sensitivity.

Main Methods:

  • In vivo studies using adenovirus to overexpress or knock down PRLR in mice.
  • In vitro experiments to assess PRLR's effect on insulin sensitivity.
  • Analysis of the signal transducer and activator of transcription-5 (STAT5) pathway.
  • Examination of PRLR expression in insulin-resistant (db/db mice) and insulin-sensitive (leucine deprivation) models.
  • Investigation of the GCN2/mTOR/S6K1 pathway in regulating PRLR expression.

Main Results:

  • Overexpression of PRLR improved insulin sensitivity, while knockdown impaired it in mouse models and in vitro.
  • The STAT5 pathway is essential for PRLR-mediated regulation of insulin sensitivity.
  • PRLR expression inversely correlated with insulin resistance, decreasing in db/db mice and increasing with leucine deprivation.
  • Altering PRLR levels reversed insulin sensitivity in both resistant and sensitive conditions.
  • Leucine deprivation increased hepatic PRLR expression via the GCN2/mTOR/S6K1 pathway.

Conclusions:

  • Hepatic PRLR has a novel function in regulating insulin sensitivity.
  • PRLR expression is subject to nutritional regulation, impacting metabolic homeostasis.
  • These findings offer new therapeutic targets for metabolic diseases related to insulin resistance.

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