Role of placental lactogens in regulating pancreatic beta-cell mass and function

胰岛含有合成胰岛素的ß细胞，胰岛素是维持正常血糖的激素。我们知道ß-细胞质量和功能是动态的，它可以通过增加ß-细胞质量和胰岛素分泌来适应怀孕等压力。我们努力研究ß-cell对环境的反应以及调节ß-cell质量和功能的机制。我们之前的研究发现，催乳素受体（Prlr）杂合缺失的小鼠，即Prlr+/-小鼠在妊娠期间的ß-细胞数量和胰岛素分泌量均低于野生型小鼠，提示作用于Prlr的胎盘乳原（PLs）对ß细胞具有生物学作用。由于Prlr缺失存在于全身，而非胰腺特异性，因此该表型可能继发于Prlr介导作用的整体减弱。为了确定妊娠期间ß-细胞适应的调节机制，我正在寻求发现PLs如何调节ß-细胞质量和功能的机制。我们的总体假设是，PLs通过其受体（即Prlr）直接作用于ß细胞，刺激增殖、胰岛素合成和分泌，以适应妊娠。

Pancreatic islets contain ß cells that synthesize insulin, the hormone responsible for maintaining normal blood glucose. We know that ß-cell mass and function is dynamic, and it can adapt to stresses such as pregnancy by increasing ß-cell mass and insulin secretion. We endeavor to study how ß-cell responds to its environment and mechanisms that regulate ß-cell mass and function. Previously, our studies have found that mice with a heterozygous deletion of prolactin receptor (Prlr), i.e. the Prlr+/- mice, had lower ß-cell number and secreted less insulin than wild type mice during pregnancy, suggesting that placental lactogens (PLs), which act on Prlr, have biological effects on ß cells. Since the Prlr deletion is in the whole body, not pancreas-specific, it is possible that the phenotype is secondary to overall diminished Prlr-mediated effects. To determine the mechanisms mediating ß-cell adaptation during pregnancy, I am seeking to discover the mechanism of how PLs regulate ß-cell mass and function. Our overall hypothesis is that PLs act directly on ß cells through its receptor (i.e. Prlr) to stimulate proliferation, insulin synthesis and secretion in adaptation to pregnancy.