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

胎盘催乳素在调节胰腺β细胞质量和功能中的作用

• 批准号: RGPIN-2015-04937
• 负责人: Huang, CarolTzuLing
• 金额: $ 1.75万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630929
• 关键词: Role; placental; lactogens; regulating; pancreatic

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.

胰岛含有合成胰岛素的胰岛细胞，胰岛素是负责维持正常血糖的激素。我们知道胰岛细胞的质量和功能是动态的，它可以通过增加胰岛细胞的质量和胰岛素分泌来适应怀孕等压力。我们奋进于研究胰岛细胞如何响应其环境和机制，调节胰岛细胞的质量和功能。以前，我们的研究发现，具有催乳素受体（Prlr）杂合缺失的小鼠，即Prlr+/-小鼠，在妊娠期间具有比野生型小鼠更低的β细胞数量和分泌更少的胰岛素，这表明作用于Prlr的胎盘催乳素（PL）对β细胞具有生物学效应。由于Prlr缺失是在整个身体中，而不是胰腺特异性的，因此该表型可能继发于总体减少的Prlr介导的作用。为了确定怀孕期间介导胰岛细胞适应的机制，我正在寻求发现PL如何调节胰岛细胞质量和功能的机制。我们的总体假设是，PL通过其受体（即Prlr）直接作用于胰岛细胞，以刺激增殖、胰岛素合成和分泌，从而适应妊娠。