Jordan Tingey, Brigham Young University
Life Sciences
Diabetes is a serious condition that is increasing worldwide. Diabetes is characterized by lost β-cell mass and uncontrolled blood glucose levels. Pancreatic islet transplantation could be used to cure people with diabetes, however the lack of islets is a major obstacle to its use. If we could understand how to increase β-cell proliferation and glucose stimulated insulin secretion (GSIS) then we could increase success in pancreatic islet transplants. Nkx6.1 induces β-cell proliferation. Nkx6.1 mediated proliferation is dependent on expression of Nr4a1 and Nr4a3. Nr4a1 and Nr4a3 are orphan nuclear receptors. It is currently unknown what ligand induces their activation. Previous reports have shown that free fatty acids induces expression of Nr4a1 and Nr4a3 in muscle, liver and adipose tissue. We show that culture of our INS-1 832/3 β -cell line in the presence of 0.2 mM palmitate induces expression of Nr4a nuclear receptors. Furthermore, culture with 0.2 mM palmitate results in increased β -cell proliferation. Finally, using INS-1 cells cultured with palmitate, and INS-1 cells deficient for either Nr4a1 or Nr4a3 we demonstrate the effect on mitochondrial respiration. Our data demonstrate that free fatty acids that are present during diabetes may induces expression and enhance activation of the Nr4a nuclear receptors, thus resulting in enhanced β -cell proliferation.