ArticleThe Journal of biological chemistry2010
Misfolded proinsulin affects bystander proinsulin in neonatal diabetes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Insulin gene mutations and posttranslational and translocation defects: associations with diabetes.Endocrine · 2020Pooled it
- JNK and p53 cause human and mouse β cell death during excessive unfolded protein response.The Journal of clinical investigation · 2026Article
- Structural Communication Between C-Peptide and Insulin Within the Proinsulin Molecule.International journal of molecular sciences · 2026Article
- 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
- Molecular puzzle of insulin: structural assembly pathways and their role in diabetes.Frontiers in cell and developmental biology · 2025Review
- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
- Macrophages and neutrophils are necessary for ER stress-induced β cell loss.Cell reports · 2022Article
- Diabetes-Associated Mutations in Proinsulin Provide a "Molecular Rheostat" of Nascent Foldability.Current diabetes reports · 2022Review
- Novel Pathogenic De Novo INS p.T97P Variant Presenting With Severe Neonatal DKA.Endocrinology · 2022Article
- Review
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
- Article
- PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones.Nature communications · 2021Article
- In celebration of a century with insulin - Update of insulin gene mutations in diabetes.Molecular metabolism · 2021Review
- Distinct states of proinsulin misfolding in MIDY.Cellular and molecular life sciences : CMLS · 2021Article
- 100 YEARS OF INSULIN: A brief history of diabetes genetics: insights for pancreatic beta-cell development and function.The Journal of endocrinology · 2021Review
- Cell death-associated lipid droplet protein CIDE-A is a noncanonical marker of endoplasmic reticulum stress.JCI insight · 2021Article
- Pharmacological Inhibition of Inositol-Requiring Enzyme 1α RNase Activity Protects Pancreatic Beta Cell and Improves Diabetic Condition in Insulin Mutation-Induced Diabetes.Frontiers in endocrinology · 2021Article
- Structural Lessons From the Mutant Proinsulin Syndrome.Frontiers in endocrinology · 2021Review
- The KINGSDiabetes · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
It has previously been shown that misfolded mutant Akita proinsulin in the endoplasmic reticulum engages directly in protein complexes either with nonmutant proinsulin or with "hProCpepGFP" (human proinsulin bearing emerald-GFP within the C-peptide), impairing the trafficking of these "bystander" proinsulin molecules (Liu, M., Hodish, I., Rhodes, C. J., and Arvan, P. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 15841-15846). Herein, we generated transgenic mice, which, in addition to expressing endogenous proinsulin, exhibit beta-cell-specific expression of hProCpepGFP via the Ins1 promoter. In these mice, hProCpepGFP protein levels are physiologically regulated, and hProCpepGFP is packaged and processed to CpepGFP that is co-stored in beta-secretory granules. Visualization of CpepGFP fluorescence provides a quantifiable measure of pancreatic islet insulin content that can be followed in live animals in states of health and disease. We examined loss of pancreatic insulin in hProCpepGFP transgenic mice mated to Akita mice that develop neonatal diabetes because of the expression of misfolded proinsulin. Loss of bystander insulin in Akita animals is detected initially as a block in CpepGFP/insulin production with intracellular accumulation of the precursor, followed ultimately by loss of pancreatic beta-cells. The data support that misfolded proinsulin perturbs bystander proinsulin in the endoplasmic reticulum, leading to beta-cell failure.
Indexed as
Identifiers
What OpenQuestion holds
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.