Date on Honors Thesis

Spring 5-2021


Biomedical Sciences


Chemistry, Psychology

Examining Committee Member

Dr. Gary ZeRuth, Advisor

Examining Committee Member

Dr. Laura Sullivan-Beckers, Committee Member

Examining Committee Member

Dr. Chris Trzepacz, Committee Member


The prevalence of type 2 diabetes continues to rise nationally and internationally, impacting millions of people worldwide. Type 2 diabetes results from insulin resistance leading to chronic hyperinsulinemia and dysfunction of the insulin producing β cells of the pancreas. While environmental factors can influence the development of type 2 diabetes, research has shown genetics are also involved. Gli-similar 3 (Glis3), a Krüppel-like zinc finger transcription factor, has been identified as a novel regulator of insulin transcription. Evidence has shown that loss-of-function Glis3 mutations decrease insulin expression, implicating Glis3 in the development of type 2 diabetes. However, the distinct role Glis3 plays in the development of type 2 diabetes remains unclear. To better understand the role of Glis3 in pancreatic β cells, we utilized the CRISPR/Cas9 system to target Glis3 for cleavage, knocking down Glis3 in the rat β cell line, INS1 832/13. Decreased Glis3 expression in rat β cells maintained under chronically elevated glucose conditions exacerbated β cell dysfunction, supporting the hypothesis that decreased Glis3 expression promotes the development of diabetes. We then applied the CRISPR/Cas9 system to knockout Glis3 in zebrafish to better understand its role in pancreatic development, β cell dysfunction, and the development of type 2 diabetes in vivo. The CRISPR/Cas9 knockout has been designed and microinjected into zebrafish, and we are currently completing the genotyping process. Taken together, the in vitro and in vivo CRISPR findings will better characterize the role of Glis3 in insulin regulation, β cell dysfunction, and the development of type 2 diabetes.