Date on Senior Honors Thesis

5-2020

Document Type

Senior Honors Thesis

Degree Name

B.A.

Department

Chemistry

Committee Chair

David Schultz

Committee Member

Richard Wittebort

Committee Member

Rohit Kulkarni

Author's Keywords

diabetes, metabolism, pancreas, differentiation, regenerative medicine

Abstract

Rebuilding or expanding the body’s ability to regulate blood glucose levels by restoring or increasing the body’s ability to produce insulin, long-term, would be a major advancement in diabetes (type-1 and type-2) treatment and could serve as a potential cure [1]. Therefore, the holy grail of diabetes treatment and cure research is to regenerate or increase the insulin producing cells in diabetic individuals (type-1 and type-2) [1, 2]. SerpinB1 has been implicated as a biomolecular signal that stimulates an increase in insulin cell mass in murine and zebrafish models that exhibit physiologically normal compensatory islet hyperplasia. In humans, SerpinB1 is hypothesized to play a similar role in the compensatory islet hyperplasia response. However, the exact role of SerpinB1 in in human compensatory islet hyperplasia is unknown. While SerpinB1 has been shown to stimulate proliferation of insulin producing beta cells in human islets [3], alternative mechanisms for SerpinB1 induced Islet growth may exist such as beta cell neogenesis from pancreatic exocrine tissue [4]. In this study, recombinant human SerpinB1 was shown to induce exocrine to endocrine transdifferentiation in human ductal cell culture models. Exocrine to endocrine transdifferentiation was marked by rhSerpinB1 induced upregulation (p<0.05) of the endocrine differentiation regulators PDX.1 and NKX2.2 at the transcript and protein levels. Upregulation of the endocrine differentiation regulators PDX-1 and NKX2.2 strongly suggest that rhSerpinB1 induces human ductal cells to differentiate down the pancreatic endocrine cell lineage [1, 3-11]. These findings suggest that in humans, SerpinB1 might stimulate exocrine to endocrine transdifferentiation to increase beta cell mass in a compensatory response. This highly novel finding must be followed up with experiments that further analyze the effects of rhSerpinB1 on human ductal cells to understand the phenomenon’s biologic and therapeutic relevance.

Lay Summary

SerpinB1 induces human non-insulin producing ductal epithelial cells of the pancreas to reprogram into cells that could become insulin producing cells.

Download

Share

COinS