Author(s): Pierce Olsen
Mentor(s): Jeffery S. Tessem
Institution BYU
It is estimated that there are 537 million people living with diabetes worldwide and 38.4 million people in the US alone (11.6% of the population). Diabetes is characterized by the loss of functional beta cell mass, a problem that is present within those that struggle with type 1 (T1D) and type 2 diabetes (T2D). Nkx6.1 is an important regulator of pancreatic beta cell development and proliferation. Nkx6.1 is sufficient to induce beta cell proliferation partly through the upregulation of CEBPA. CEBPA is sufficient to induce beta cell proliferation and protect beta cells from stress that induces the unfolded protein response (UPR). The UPR is triggered by the accumulation of misfolded proteins within the endoplasmic reticulum (ER) and is sufficient to induce β-cell apoptosis. While UPR activation is generally thought to be associated with glucolipotoxicity, β-cells exposed to proinflammatory cytokines such as those present in T1D are sufficient to induce ER stress and activate the UPR. Given our previous data that CEBPA overexpression protects beta cells from glucolipotoxicity induced ER stress and UPR activation, we show that CEBPA overexpression can attenuate the ER stress and UPR activation induced by inflammatory cytokine exposure. We purposed to determine if CEBPA is sufficient to protect beta cells against cytokine mediated ER stress and UPR, and if this occurs through the same pathways we have previously shown for glucolipotoxicity mediated ER stress. Understanding the ability of CEBPA to protect against cytokine mediated ER stress will allow us to design novel therapies to protect beta cells of individuals with T1D.