Prolactin as an Adjunct to Anti-CD3 Type I Diabetes Therapy

Abstract

Type 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.