Huang, Carol T. L.Makkar, Guneet2018-06-252018-06-252018-06-15Makkar, G. (2018). Novel signaling target of prolactin receptor in pancreatic β-cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32005http://hdl.handle.net/1880/106779Prolactin receptor mediated β-cell mass adaptation is essential for glucose homeostasis during pregnancy. In this study, we have identified Lrrc55 as a novel downstream target of prolactin receptor in pancreatic β-cells. Lrrc55 is an auxiliary subunit of BK channels which is expressed in pancreatic islets at a very low level. During pregnancy, Lrrc55 undergoes ~70 fold increase in its expression and this increase is restricted to β-cells. Exposure of islets to diabetic milieu for 12-48 hrs led to an increase in the expression of Lrrc55, although the change was not as dramatic as that seen during pregnancy. We did not observe any change in the mRNA levels of BK channel and other paralogues of Lrrc55 during pregnancy or by induction of cellular stress. Lrrc55 also protected the islets against glucolipotoxicity-induced apoptosis by attenuating pro-apopotic components such as IRE1α, CHOP, Caspase-9 and upregulating pro-survival components like BIP, Bcl-2 of the ER stress pathway. Lrrc55’s association with BK channels led us to investigate its role in insulin secretion from β-cells. We observed minimal modulation by Lrrc55 in insulin release from β-cells. Taken together, our results put forth Lrrc55 as a novel pro-survival factor in pancreatic β-cells.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.diabetesprolactinLrrc55Education--SciencesGeneticsBiology--MolecularBiochemistrymaster thesis10.11575/PRISM/32005