Abstract:
:Given the functional importance of the endoplasmic reticulum (ER), an organelle that performs folding, modification, and trafficking of secretory and membrane proteins to the Golgi compartment, the maintenance of ER homeostasis in insulin-secreting β-cells is very important. When ER homeostasis is disrupted, the ER generates adaptive signaling pathways, called the unfolded protein response (UPR), to maintain homeostasis of this organelle. However, if homeostasis fails to be restored, the ER initiates death signaling pathways. New observations suggest that both chronic hyperglycemia and hyperlipidemia, known as important causative factors of type 2 diabetes (T2D), disrupt ER homeostasis to induce unresolvable UPR activation and β-cell death. This review examines how the UPR pathways, induced by high glucose and free fatty acids (FFAs), interact to disrupt ER function and cause β-cell dysfunction and death.
journal_name
Annu Rev Biochemjournal_title
Annual review of biochemistryauthors
Back SH,Kaufman RJdoi
10.1146/annurev-biochem-072909-095555subject
Has Abstractpub_date
2012-01-01 00:00:00pages
767-93eissn
0066-4154issn
1545-4509journal_volume
81pub_type
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