Abstract:
:The early steps of insulin biosynthesis occur in the endoplasmic reticulum (ER), and the beta-cell has a highly developed and active ER. All cells regulate the capacity of their ER to fold and process client proteins and they adapt to an imbalance between client protein load and folding capacity (so-called ER stress). Mutations affecting the ER stress-activated pancreatic ER kinase (PERK) and its downstream effector, the translation initiation complex eukaryotic initiation factor 2 (eIF2), have a profound impact on islet cell development, function, and survival. PERK mutations are associated with the Wolcott-Rallison syndrome of infantile diabetes and mutations that prevent the alpha-subunit of eIF2 from being phosphorylated by PERK, block beta-cell development, and impair gluconeogenesis. We will review this and other rare forms of clinical and experimental diabetes and consider the role of ER stress in the development of more common forms of the disease.
journal_name
Diabetesjournal_title
Diabetesauthors
Harding HP,Ron Ddoi
10.2337/diabetes.51.2007.s455subject
Has Abstractpub_date
2002-12-01 00:00:00pages
S455-61eissn
0012-1797issn
1939-327Xjournal_volume
51 Suppl 3pub_type
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