Huang, CarolShrivastava, Vipul2016-05-202016-05-2020162016Shrivastava, V. (2016). The Role of Prolactin Receptors in Regulation of Pancreatic Beta Cell Mass and Function (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28348http://hdl.handle.net/11023/3032During pregnancy, pancreatic β-cells adapt to the increase in maternal insulin resistance by up-regulating β-cell mass, insulin synthesis, and lowering glucose-stimulated insulin secretion threshold. Signaling through prolactin receptor (PrlR) is critical for these adaptive responses. We hypothesize that PrlR present on β-cells are the primary determinant of β-cell adaptation to pregnancy. We found that β-cell specific deletion of PrlR in mice leads to higher fasted blood glucose and impaired glucose tolerance in comparison with wild type mice. Furthermore, we identified Lrrc55 (leucine rich repeat containing 55), an auxiliary subunit of BK channels as one of the potentially novel targets of PrlR. Results suggest that Lrrc55 overexpression protected INS-1 cells from H2O2, high glucose, palmitate, and high glucose+palmitate-induced apoptosis by attenuating ER stress and intrinsic apoptosis pathways and also maintaining healthy ER calcium reserves. Taken together, this study helps unravel components of PrlR signaling as possible therapeutic strategy to treat diabetes.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.BiologyBioinformaticsBiostatisticsBiology--CellGeneticsDiabetesmaster thesis10.11575/PRISM/28348