Astaxanthin-S-Allyl Cysteine Ester Protects Pancreatic β-Cell From Glucolipotoxicity by Suppressing Oxidative Stress, Endoplasmic Reticulum Stress and mTOR Pathway Dysregulation

Glucolipotoxicity (GLT) has emerged as established mechanism in the progression of diabetes. Identifying compounds that mitigate GLT-induced deleterious effect on β-cells are considered important strategy to overcome diabetes. Hence, in the present study, astaxanthin-s-allyl cysteine (AST-SAC) diester was studied against GLT in β-cells. Mus musculus pancreatic β-cell line (βTC-tet) was treated with high glucose (25 mM; HG) and 95 μM palmitate (PA) for 24 h to induce GLT. AST-SAC at various concentrations (5, 10, and 15 μg/ml) were treated to understand the protective effect against HG + PA exposure in β-cells. Under HG + PA exposure conditions oxidative stress, deregulation of mTOR pathway and endoplasmic reticulum (ER) stress are witnessed. AST-SAC treatment eased oxidative stress, mitochondrial depolarization, DNA damage, calcium overload and accumulation of autophagosome against HG + PA exposure conditions thereby protected the cell viability of β-cells. AST-SAC maintained the level of proteins involved in mTOR pathway under HG + PA exposure conditions. Also, AST-SAC treatment has mitigated the increased expression of genes and proteins such as IRE1 and PERK involved in ER stress-mediated unfolded protein response (UPR) signaling pathways. In correspondence to it, the expression of genes involved in insulin secretion was preserved by AST-SAC. Due to these protective effects of AST-SAC the insulin secretion was well-maintained in β-cells under HG + PA exposure conditions. AST-SAC through normalizing antioxidant status and mTOR axis as well as preventing the harmful effect of ER-stress mediated UPR pathway has promoted the β-cell survival and insulin secretion against GLT. Simultaneously targeting oxidative stress/mTOR axis/ER stress is required to efficiently overcome GLT in β-cells.