Author(s): Trevor Kendrick
Mentor(s): Jeffery S. Tessem
Institution BYU
Diabetes is a chronic metabolic disease characterized by an inability of beta cells to produce or secrete insulin due to decreasing beta cell mass, a condition induced by beta cell death or overuse. Beta cells typically stop replicating after an individual reaches puberty, but have been seen to proliferate under certain circumstances, including when nuclear transcription factor Nkx6.1 is overexpressed. We have shown that Sirtuin 7 (Sirt7), a deacetylase located in the nucleus, directly interacts with Nkx6.1, a transcription factor essential for beta cell function and proliferation. We have shown that one of the post translational modifications that impinges on Nkx6.1 activity is acetylation. Given Sirt7’s role as a deacetylase, and published reports demonstrating its impact on glucose stimulated insulin secretion (GSIS), we hypothesized that the interaction between Nkx6.1 and Sirt7 may be needed for the Nkx6.1 mediated enhancement of glucose stimulated insulin secretion. Here we present data regarding the interaction between Nkx6.1 and Sirt7 in terms of Nkx6.1 acetylation status, the effect on GSIS, and the effect of cultured glucose concentration on this interaction. These findings may be leveraged to develop interventions to better treat patients with type 1 and type 2 diabetes.