Stearoyl-CoA desaturase (SCD) is a highly expressed enzyme in primary human β-cells that is involved in PA metabolism and has a protective role against lipotoxicity in β-cells. SCD catalyzes insertion of the double bond at the delta-9 position of 12-19 carbon in saturated fatty acids, thereby converting them to MUFAs. SCD controls intracellular SFA/MUFA equilibrium, which is physiologically crucial for proper β-cell function given the cytotoxicity of long-chain SFAs higher than long-chain MUFAs.
It has been observed that SCD ablation is associated with β-cell failure and T2D development and results in lower GSIS, proliferation, and apoptosis induction in β-cells. Importantly, SCD gene expression is lower in β-cell enriched tissue from individuals with T2D compared with healthy donors. It has been proposed that, over time, in the course of T2D progression, SCD expression by β-cells is first induced during compensation in response to IR, and as the duration of diabetes increases, SCD expression decreases leading to a decline in β-cell function. Inhibition of SCD activity affects autophagosome-lysosome fusion through perturbations in cellular membrane integrity, leading to an aberrant stress response and β-cell failure and alters DNA methylation levels in 3T3-L1 adipocytes.
