Lipotoxic Stress Induces Pancreatic β-Cell Apoptosis through Modulation of Bcl-2 Proteins by the Ubiquitin-Proteasome System

Figure 8

Proposed model for the role of UPS inactivation in palmitate-induced β-cell apoptosis. Palmitate induces inactivation of the UPS in β-cells resulting in increased ubiquitinated proteins, ER stress, and posttranscriptional inactivation of Bcl-2 and other prosurvival Bcl-2 proteins. In addition, AKT is dephosphorylated leading to upregulated expression of the BH3-only protein PUMA. These signals converge on mitochondrial permeabilization causing β-cell demise.