Kyle Kener, Brigham Young University
Life Sciences
Diabetes is characterized by the inability to maintain a normal blood glucose level caused by decreased insulin due to β-cell loss, or decreased insulin sensitivity in the liver, muscle, and adipose tissue. While β-cell death is a hallmark of T1D, β-cells are also destroyed as T2D progresses. Death of β-cells is eventually a hallmark of both forms of diabetes. This results in decreased functional β-cell mass, which is defined by the ability to secrete insulin while maintaining β-cell number through proliferation or decreased apoptosis. To resolve the decreased β-cell level, much research is being done regarding β-cell proliferation to increase pancreatic β-cell mass. However, another important step in this process is protecting β-cells from apoptotic mediated β-cell death. The β-cell transcription factor Nkx6.1 is sufficient to induce β-cell proliferation and increase protection against apoptotic insults. The Nkx6.1 target gene VGF is critical for protection against apoptosis. Our data demonstrates that Nkx6.1 upregulates expression of c-Fos. Furthermore, we show that c- Fos is sufficient to induce expression of VGF. In addition, our data demonstrates that expression of c-Fos is sufficient to protect β-cells from apoptotic insults. Our data demonstrates that c-Fos is the link between the Nkx6.1 and VGF, and that it’s expression is sufficient to protect rat pancreatic β-cells from apoptosis.