VI- Conclusions

Maintaining the ER homeostasis is critical for the cell function and survival. Under physiological conditions, UPR signaling may play an important role for beta-cell development. However, prolonged and/or excessive activation of UPR signaling can have detrimental effects leading to beta-cell dysfunction and death, and could become an underlying factor for diabetes. While lipotoxicity and glucotoxicity may both be ER stress triggering factors in the context of type 2 diabetes, viral infections, defective arrangement of MHC molecules at ER, or deregulated antigen presentation due to altered function of ER associated degradation pathways, might be critical for the pathogenesis of type 1 diabetes. Alleviating ER stress by blocking accumulation of misfolded proteins and/or improving folding capacity or reducing the oxidative stress that is generated during disulphide formation are important potential therapeutic strategies for the ER stress-related diseases.1

“The Stressed Beta-Cell”
I- ER and the canonical unfolded protein response (UPR)
II- When UPR leads to cell death
III- Cellular stress in type 2 diabetes
IV- The mitochondria and cellular stress
V- Therapeutic targeting of ER dysfunction
VI- Conclusions