The antioxidant, N-acetyl-L-cysteine, affects beta cell oxidative stress, insulin secretion, and intracellular signaling pathways in MIN6 cells.

There is intense public interest in the potential of antioxidant supplements as a preventative treatment for conditions associated with increased oxidative stress, such as type 2 diabetes mellitus. However, there is limited evidence regarding the effects of antioxidants on beta cells during physiological and pathological conditions. We examined the direct effects of N-acetyl-L-cysteine (NAC) supplementation on the MIN6 beta cell line under physiological and fatty acid stress conditions. MIN6 cells were cultured in growth medium with or without NAC (physiological conditions) or growth medium plus palmitate with or without NAC (fatty acid stress conditions). We observed that MIN6 cells receiving NAC, under physiological or fatty acid stress conditions, displayed significantly reduced cellular ATP content and oxidative stress without changes to markers of cell proliferation or apoptosis. Regardless of the treatment conditions, NAC lowered basal insulin release with no change to cellular insulin content, yet improved high glucose-stimulated insulin secretion (GSIS) was only observed under physiological conditions. Importantly, phosphorylated AKT was significantly reduced with NAC supplementation under physiological and fatty acid stress conditions, which was inversely proportional to ERK1/2Thr202/Tyr204 phosphorylation during fatty acid stress. Our findings provided evidence that NAC directly impacts ATP production and insulin signaling pathways in MIN6 cells. This study highlights the importance of investigating ROS balance in pancreatic beta cells under physiological and pathological conditions to determine if antioxidant therapies can improve functionality without interfering with essential signaling processes.