ArticleProceedings of the National Academy of Sciences of the United States of America2007
Proinsulin maturation, misfolding, and proteotoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
107 citing papers in PubMed, 164 citations in OpenAlex.
- Polyadenylation of insulin mRNA by Tent5a regulates pancreatic beta cells.Nature communications · 2026Article
- Structural Communication Between C-Peptide and Insulin Within the Proinsulin Molecule.International journal of molecular sciences · 2026Article
- Trapα deficiency impairs the early events of insulin biosynthesis and glucose homeostasis.The Journal of clinical investigation · 2025Article
- Synthetic studies of the mutant proinsulin syndrome demonstrate correlation between folding efficiency and age of diabetes onset.International journal of peptide research and therapeutics · 2025Article
- Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering.The EMBO journal · 2024Article
- Casting Light on the Janus-Faced HMG-CoA Reductase Degradation Protein 1: A Comprehensive Review of Its Dualistic Impact on Apoptosis in Various Diseases.Molecular neurobiology · 2024Review
- A metabolic redox relay supports ER proinsulin export in pancreatic islet β cells.JCI insight · 2024Article
- EDEM1 regulates the insulin mRNA level by inhibiting the endoplasmic reticulum stress-induced IRE1/JNK/c-Jun pathway.iScience · 2023Article
- β Cell and Autophagy: What Do We Know?Biomolecules · 2023Review
- Harnessing Human Pluripotent Stem Cell-Derived Pancreatic In Vitro Models for High-Throughput Toxicity Testing and Diabetes Drug Discovery.Handbook of experimental pharmacology · 2023Article
- Visualizing the Nucleome Using the CRISPR-Cas9 System: From in vitro to in vivo.Biochemistry. Biokhimiia · 2023Review
- IER3IP1 is critical for maintaining glucose homeostasis through regulating the endoplasmic reticulum function and survival of β cells.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Carbonyl Posttranslational Modification Associated With Early-Onset Type 1 Diabetes Autoimmunity.Diabetes · 2022Article
- ER remodeling via ER-phagy.Molecular cell · 2022Review
- Diabetes-Associated Mutations in Proinsulin Provide a "Molecular Rheostat" of Nascent Foldability.Current diabetes reports · 2022Review
- Peptide Model of the Mutant Proinsulin Syndrome. I. Design and Clinical Correlation.Frontiers in endocrinology · 2022Article
- ER Redox Homeostasis Regulates Proinsulin Trafficking and Insulin Granule Formation in the Pancreatic Islet β-Cell.Function (Oxford, England) · 2022Article
- Peptide Model of the Mutant Proinsulin Syndrome. II. Nascent Structure and Biological Implications.Frontiers in endocrinology · 2022Article
- Progressive endoplasmic reticulum stress over time due to human insulin gene mutation contributes to pancreatic beta cell dysfunction.Diabetologia · 2021Article
- PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones.Nature communications · 2021Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
As a tool to explore proinsulin (PI) trafficking, a human PI cDNA has been constructed with GFP fused within the C peptide. In regulated secretory cells containing appropriate prohormone convertases, the hProCpepGFP construct undergoes endoproteolytic processing to CpepGFP and native human insulin, which are specifically detected and cosecreted in parallel with endogenous insulin. Expression of C(A7)Y mutant PI results in autosomal dominant diabetes in Akita mice. We directly identify the misfolded PI in Akita islets and also show that C(A7)Y mutant PI, either in the context of the hProCpepGFP chimera or not, engages directly in protein complexes with nonmutant PI, impairing the trafficking and recovery of nonmutant PI. This trapping mechanism decreases insulin production in beta cells. Thereafter we observe a loss of beta cell viability. The data imply that PI misfolding leading to impaired endoplasmic reticulum exit of nonmutant PI may be a key early step in a chain reaction of beta cell dysfunction and demise leading to onset and progression of diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.