ArticleMolecular and cellular endocrinology2019
Defective endoplasmic reticulum export causes proinsulin misfolding in pancreatic β cells.
Article in Molecular and cellular endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- HNF1A and A1CF coordinate a beta cell transcription-splicing axis that is disrupted in type 2 diabetes.Cell metabolism · 2025Article
- Maturity-Onset Diabetes of the Young 10 (MODY10): A Comprehensive Review of Genetics, Clinical Features, and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Molecular puzzle of insulin: structural assembly pathways and their role in diabetes.Frontiers in cell and developmental biology · 2025Review
- Exploring proinsulin proteostasis: insights into beta cell health and diabetes.Frontiers in molecular biosciences · 2025Review
- Proinsulin folding and trafficking defects trigger a common pathological disturbance of endoplasmic reticulum homeostasis.Protein science : a publication of the Protein Society · 2024Article
- EDEM1 regulates the insulin mRNA level by inhibiting the endoplasmic reticulum stress-induced IRE1/JNK/c-Jun pathway.iScience · 2023Article
- Pancreatic beta cell ER export in health and diabetes.Frontiers in endocrinology · 2023Review
- The First Pituitary Proteome Landscape From Matched Anterior and Posterior Lobes for a Better Understanding of the Pituitary Gland.Molecular & cellular proteomics : MCP · 2023Article
- Cargo receptor Surf4 regulates endoplasmic reticulum export of proinsulin in pancreatic β-cells.Communications biology · 2022Article
- Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.The Journal of clinical investigation · 2021Review
- Biological behaviors of mutant proinsulin contribute to the phenotypic spectrum of diabetes associated with insulin gene mutations.Molecular and cellular endocrinology · 2020Article
- Raptor determines β-cell identity and plasticity independent of hyperglycemia in mice.Nature communications · 2020Article
- Role of Proinsulin Self-Association in MutantDiabetes · 2020Article
- Misfolded proinsulin impairs processing of precursor of insulin receptor and insulin signaling in β cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Endoplasmic reticulum (ER) homeostasis is essential for cell function. Increasing evidence indicates that, efficient protein ER export is important for ER homeostasis. However, the consequence of impaired ER export remains largely unknown. Herein, we found that defective ER protein transport caused by either Sar1 mutants or brefeldin A impaired proinsulin oxidative folding in the ER of β-cells. Misfolded proinsulin formed aberrant disulfide-linked dimers and high molecular weight proinsulin complexes, and induced ER stress. Limiting proinsulin load to the ER alleviated ER stress, indicating that misfolded proinsulin is a direct cause of ER stress. This study revealed significance of efficient ER export in maintaining ER protein homeostasis and native folding of proinsulin. Given the fact that proinsulin misfolding plays an important role in diabetes, this study suggests that enhancing ER export may be a potential therapeutic target to prevent/delay β-cell failure caused by proinsulin misfolding and ER stress.
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