4. Conclusion

Because of the importance of insulin in diabetes mellitus, insulin secretory pathway has been extensively studied. Recent advance in the understanding of biosynthetic pathway reveals the importance of ER stress in β-cell dysfunction and novel machineries of secretory granule biogenesis. However, still many questions remain. What are the mechanisms by which ER-stress sensors regulate proinsulin translation and folding? Is it relevant to prevent β-cell death by preventing UPR? The inhibition of CHOP has been studied to prevent β-cell death for the treatment of diabetes [46, 107–109]; however, it should be addressed carefully that even if β-cells survive by preventing CHOP, and too much accumulation of unfolded proteins in the ER may prevent normal proinsulin folding and would not support the function of islets of Langerhans. Decreasing the continuous high demand of insulin synthesis is anyway the primary importance for diabetes; then thinking about how to support proinsulin folding, packaging proinsulin into secretory granules, and elimination of unfolded proteins from β-cells would help for developing new treatments of diabetes.
