Chronic Exposure to Palmitic Acid Downregulates AKT in Beta-Cells through Activation of mTOR

High circulating lipids occurring in obese individuals and insulin resistant patients are considered a contributing factor to Type 2 Diabetes (T2D). Exposure to high lipids is proposed to both protect and damage beta-cells under different circumstances. By feeding mice high fat diet (HFD) for 2 weeks up to 14 months, we showed that HFD initially causes the beta-cells to expand in population whereas long-term exposure to HFD is associated with failure of beta-cells and the inability of animals to respond to glucose challenge. To prevent the failure of beta-cells and the development of T2D, we explored the molecular mechanisms that underlie this biphasic response of beta-cells to lipid exposure. Using palmitic acid (PA) in cultured beta-cells and islets, we demonstrated that chronic exposure to lipids leads to reduced viability and inhibition of cell cycle progression concurrent with downregulation of a pro-growth/survival kinase AKT, independent of glucose. To explore the mechanism further, we performed RNA-seq analysis in WT and AKT1-/- mice fed HFD for 4 months. The data here is the results of this study. In this study, we fed 3 month old mice with high fat diet (60% kcal% FAT) for 4 months. Islets were isolated and extracted for RNA. RNA was sent to the equences.