Shawn Meng

Pancreatic islets are clusters of primarily endocrine cells, most notably, insulin-secreting beta cells. Restoring insulin production through increased beta cell presence, and subsequently, increased islet growth, is currently being explored as a method of fighting Type 1 diabetes. Previously, our lab has shown that inhibiting serpinB13, a serine protease inhibitor, in the pancreas significantly increases differentiation of endocrine progenitor cells into beta cells by dismantling the Notch signaling pathway, leading to increased expression of cell fate determining transcription factors such as neurogenin3. Advancing this study, we created a SERPINB13 knock-out mouse model to further elucidate the relationship between serpinB13 and beta cells by assessing the impact of permanent removal of serpinB13 function. Analysis of 3-week-old heterozygous and homozygous knock-out mice revealed that heterozygous knock-out mice exhibit significant increase in the number of small pancreatic islets compared to wild-type controls. Conversely, analysis of 8-week-old heterozygous and homozygous knock-out mice revealed significant decrease in the number of medium and larger islets compared to wild-type controls. Together, these results suggest that serpinB13 performs a dual role in the development of pancreatic beta cells. While the absence of serpinB13 promotes differentiation of progenitor cells into beta cells, the presence of serpinB13 appears to be critical for the subsequent growth and survival of these cells as a mouse ages. Thus, we propose that inhibition of serpinB13 early in life followed by the later reintroduction of functional serpinB13 may offer a novel approach to promoting sustained beta cell proliferation and survival.