Author(s): Kyla King
Mentor(s): Jeffery S. Tessem
Institution BYU
A total of 38.4 million Americans suffer from Type 1 or Type 2 diabetes (T1D or T2D), which is about 11.6% of the population. Diabetes is one of the leading causes of death for Americans. A distinctive characteristic of T1D and T2D is decreased functional beta cell mass. Functional beta cell mass refers to the total number of insulin-producing beta cells in the pancreas. Healthy beta cells are measured by beta cell proliferation rates, insulin secretion rates, and their ability to protect against apoptosis. We have shown that the transcription factor Nr4a1 is adequate to enhance beta cell proliferation and glucose-stimulated insulin secretion (GSIS). However, Nr4a1 expression and activity are decreased in diabetic individuals. Thus, processes that increase the expression of Nr4a1 could result in greater functional beta cell mass. Studies on human acute myeloid leukemia have shown that the FDA-approved drug alprostadil can increase Nr4a1 expression. We hypothesized that beta cells treated with alprostadil would show enhanced expression of Nr4a1, increased expression of Nr4a1 target genes, and higher rates of beta cell proliferation and glucose-stimulated insulin secretion (GSIS). Here we present the effect of alprostadil treatment on beta cell Nr4a1 expression. Additionally, we show the impacts of alprostadil on Nr4a1 target gene expression, beta cell proliferation, and GSIS. These findings may be leveraged to develop better treatments for the millions affected by Type 1 and Type 2 diabetes.