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A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
Published on: June 25, 2018
Astaxanthin-S-Allyl Cysteine Ester Protects Pancreatic β-Cell From Glucolipotoxicity by Suppressing Oxidative Stress,
Penislusshiyan Sakayanathan1,2, Chitra Loganathan3, Palvannan Thayumanavan1
1Department of Biochemistry, Periyar University, Salem, India.
Abstract:
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.
Insights
Astaxanthin-s-allyl cysteine (AST-SAC) diester protects pancreatic beta cells from glucolipotoxicity (GLT). This compound mitigates oxidative stress, endoplasmic reticulum stress, and preserves insulin secretion, offering a potential strategy against diabetes progression.
Area of Science:
- Endocrinology
- Cell Biology
- Pharmacology
Background:
- Glucolipotoxicity (GLT) is a key factor in diabetes development, damaging pancreatic beta cells.
- Identifying protective compounds is crucial for managing diabetes and its complications.
Purpose of the Study:
- To investigate the protective effects of astaxanthin-s-allyl cysteine (AST-SAC) diester against GLT-induced damage in mouse pancreatic beta cells.
- To elucidate the mechanisms underlying AST-SAC's protective action.
Main Methods:
- Mouse pancreatic beta cells (βTC-tet) were exposed to high glucose and palmitate to induce GLT.
- Cells were treated with varying concentrations of AST-SAC.
- Assessed oxidative stress, mitochondrial function, DNA damage, ER stress, mTOR pathway, and insulin secretion.
Main Results:
- AST-SAC treatment significantly protected beta cell viability against GLT.
- It reduced oxidative stress, DNA damage, and ER stress markers (IRE1, PERK).
- AST-SAC maintained mTOR pathway protein levels and preserved insulin secretion.
Conclusions:
- AST-SAC effectively protects pancreatic beta cells from GLT by normalizing antioxidant status, the mTOR axis, and mitigating ER stress.
- AST-SAC demonstrates potential as a therapeutic agent for managing diabetes by promoting beta cell survival and function.
