Parker Booren; Talon Aitken; Samuel Grover; Nathan Jensen; Jackie Crabree, Brigham Young University
There are 1.5 million Americans diagnosed with diabetes each year. A key characteristic of both type 1 and type 2 diabetes mellitus is the lack or severely reduced number of β cells. This impairment leads to a lack of insulin, which prevents the body from using glucose and the body suffers from this lack of sustenance. Finding a way to cause the existing β cells to proliferate would fix insulin production and ultimately cure diabetes. A problem with this fix is that proliferation in β cells stops somewhere during adolescence. Nkx6.1 is a transcription factor that has been shown to induce β cell proliferation and enhance insulin secretion in young β cells through upregulating Nr4a1, Nr4a3, and VGF. Interestingly, Nkx6.1 is unable to induce these same changes in aged β cells. The reason for this difference between young and aged β cells is unknown. However, one possibility is epigenetic modification at Nkx6.1 binding sites necessary for inducing proliferation and enhancing insulin secretion. Here we present data regarding Nkx6.1 binding at the Nr4a1, Nr4a3 and VGF promoters, as well as epigenetic analysis at these same promoters in young and aged β cells. These results begin to address why young and aged β cells react so differently in respect to Nkx6.1 mediated increases in functional β cell mass.