Indiana University-Purdue University Indianapolis (IUPUI) / Diabetes occurs as a result of the failure of pancreatic insulin-producing β cells.
The preservation or renewal of β cells is a strategy that can prevent diabetes by targeted
manipulation of mechanisms associated with autoimmune β cell destruction or β cell
regeneration. ErbB signaling, specifically epidermal growth factor receptor (EGFR)
signaling, is associated with cell survival, growth, and proliferation. Thus, we
investigated the role of the ErbB inhibitor, mitogen-inducible gene 6 (mig6), in pancreas
development and in the progression to diabetes. Using morpholino knockdown in a
zebrafish model of development, we discovered that mig6 is required for the generation
of α and β cells as well as the formation of the exocrine pancreas. We suspect that the
loss of mig6 function causes premature differentiation of ductal progenitor cells, and acts
as a switch between progenitor differentiation and endocrine transdifferentiation.
Furthermore, we established a pancreas-specific mig6 knockout mouse that maintained
glucose tolerance and had a higher β cell mass after chemically-induced β cell injury by
way of increased β cell proliferation. Our data suggests that mig6 is required during
pancreas development and may be employed as a switch to direct the production of new β
cells, but that during adulthood, it is detrimental to the recovery of β cell mass, making it
a therapeutic target for β cell preservation after the onset of diabetes.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/17763 |
| Date | 14 August 2018 |
| Creators | El, Kimberley Mei Ling |
| Contributors | Fueger, Patrick T., Pavalko, Fred M., Anderson, Ryan M., Dong, X. Charlie, Haneline, Laura S. |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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