Skip to main content
Utah's Foremost Platform for Undergraduate Research Presentation
2018 Abstracts

Barriers to the proliferation of aged β cells through overexpression of Nkx6.1

Parker Booren; Nathanael Jensen; Talon Aitken; Samuel Grover; Jackie Crabree, Brigham Young University

Diabetes continues to grow at a rapid rate, affecting the lives of both young and old. Both Type 1 and Type 2 diabetes lead to eventual β cell depletion (and subsequent decrease in insulin secretion). This can be treated through β cell transplantation from the pancreata of cadavers. Currently, collecting sufficient β cells for one diabetic patient requires pancreata from multiple cadavers. If proliferation can be induced in a donor’s aged β cells, transplantation would become more effective as one donor now becomes sufficient to serve one or two patients. Nkx6.1 is a transcription factor that increases insulin secretion and induces proliferation of young rat β cells (5 weeks) through the upregulation of its target genes: VGF, Nr4a1 and Nr4a3. Aged rat β cells (5+ months) fail to proliferate after overexpression of Nkx6.1. We have also shown that upregulation of Nkx6.1’s target genes is disrupted in these aged β cells. This may be due to changes in expression of a binding partner necessary for Nkx6.1’s upregulation of these target genes or to changes in Nkx6.1 posttranslational modifications that impede binding partner interactions in aged β cells. We present data from co-immunoprecipitation and mass spectrometry experiments that reveal the presence or absence of Nkx6.1’s binding partner in young and aged β cells. Furthermore, we present mass spectrometry results of Nkx6.1 posttranslational modification from young and old β cells. This data will increase understanding on the ability of Nkx6.1 to upregulate its target genes in an aged β cell.