Huang, CarolHyslop, Colin2014-10-092014-11-172014-10-092014Hyslop, C. (2014). Prolactin as an Adjunct to Anti-CD3 Type I Diabetes Therapy (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27455http://hdl.handle.net/11023/1927Type I diabetes is caused by autoimmune destruction of ß-cells. While immune therapy halts autoimmune attack on ß-cells, the residual ß-cell number is often insufficient for euglycemia. We hypothesize that addition of a growth factor to increase β-cell number will be more effective at reversing hyperglycemia than immune therapy alone. We chose prolactin because it stimulates ß-cell proliferation and insulin synthesis in vivo. In this study, we found that diabetic NOD mice treated with anti-CD3 and prolactin achieved a higher diabetes remission rate in comparison to those treated with anti-CD3 alone. Mice treated with anti-CD3 and prolactin had higher pancreatic insulin content and secreted more insulin during a glucose tolerance test. They had higher ß-cell mass and number due to a higher ß-cell proliferation rate. Furthermore, the anti-CD3 and prolactin treated group had a higher proportion of insulitis-free islets. We found no evidence of ß-cell neogenesis and even the addition of exendin-4, a growth factor analagoue thought to be able to induce β-cell neogenesis, failed to induce β-cell neogenesis. Therefore, this study suggests that the paradigm of using a growth factor to stimulate ß-cell proliferation and expand ß-cell number in conjunction with immune therapy is potentially an effective strategy to treat type 1 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.Biochemistryprolactintype I diabetesanti-CD3master thesis10.11575/PRISM/27455