The highly developed endoplasmic reticulum (ER) structure is one of the characteristic features of pancreatic beta-cells. Recent study showed that ER stress causes beta-cell dysfunction. However, little is known about the effects of high glucose concentration on induction of ER stress in pancreatic beta-cells. Therefore, this study was designed to evaluate whether exposure of high glucose concentration in ratinsulinomacell line, INS-1 cell induces ER stress and whether ER stress decreases insulingene expression.
The prolonged exposure of INS-1 cells with the 30 mM glucose concentration decreased insulinmRNA expression in a time dependent manner and impaired GSIS while did not influence on cell viability. 30 mM glucose increased phosphorylation of eIF2alpha, XBP-1 splicing and CHOP expression in INS-1 cells. Tunicamycin-treated INS-1 increased XBP-1 splicing and decreased insulinmRNA expression in a dose dependent manner.
CONCLUSION:
This study showed that prolonged exposure of INS-1 with high glucose concentration induces ER stress and ER stress decreases insulingene expression. Further studies about underlying molecular mechanism by which ER stress induces beta-cell dysfunction are needed.