Author(s): Jonathan Hanson
Mentor(s): Jeffery S. Tessem
Institution BYU
Gestational Diabetes Mellitus (GDM) is characterized by the inability of a mother’s β-cells to meet glucose demands during pregnancy. Insufficient functional β-cell mass and reduced insulin sensitivity cause hyperglycemia, which can have deleterious effects on both mother and fetus. There is evidence that hormones such as prolactin (placental lactogen) play an important role in regulating β-cell proliferation during pregnancy. Previous studies indicate that prolactin induces the transcription factor Nr4a1, which is known to upregulate β-cell proliferation. We have shown that Nr4a1 regulates downstream expression of the target genes Glut2, Ndufa4, Ins1, and Ins2, which are factors critical to insulin secretion. Furthermore, we have shown that Nr4a1 overexpression is sufficient to induce β-cell proliferation, and Nr4a1 deletion impairs β-cell proliferation. However, it remains to be seen if prolactin induces these downstream factors, and if the expression is dependent on Nr4a1. We hypothesize that prolactin treatment mediated β-cell proliferation is dependent on Nr4a1. Here we present the effects of prolactin treatment on wild type and Nr4a1 deficient β-cells in terms of Nr4a1 expression, Nr4a1 activity, and β-cell proliferation and glucose stimulated insulin secretion. These results provide us with a greater understanding of the mechanisms that mediate prolactin-induced β-cell proliferation in pregnancy and suggests how this pathway can be manipulated to develop treatments for GDM.