ArticleBiochemical and biophysical research communications2010
Mutant proinsulin proteins associated with neonatal diabetes are retained in the endoplasmic reticulum and not efficiently secreted.
Article in Biochemical and biophysical research communications, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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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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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Insulin gene mutations and posttranslational and translocation defects: associations with diabetes.Endocrine · 2020Pooled it
- Exploring proinsulin proteostasis: insights into beta cell health and diabetes.Frontiers in molecular biosciences · 2025Review
- Loss of Preproinsulin Interaction with Signal Recognition Particle Activates Protein Quality Control, Decreasing mRNA Stability.Journal of molecular biology · 2024Article
- Pathogenic signal peptide variants in the human genome.NAR genomics and bioinformatics · 2023Article
- A Review of the Biosynthesis and Structural Implications of Insulin Gene Mutations Linked to Human Disease.Cells · 2023Review
- Understanding Insulin in the Age of Precision Medicine and Big Data: Under-Explored Nature of Genomics.Biomolecules · 2023Review
- Acute Recurrent Pancreatitis in a Child With INS-Related Monogenic Diabetes and a Heterozygous Pathogenic CFTR Mutation.Journal of the Endocrine Society · 2023Article
- Insights into the Genetics and Signaling Pathways in Maturity-Onset Diabetes of the Young.International journal of molecular sciences · 2022Review
- UDP-glucose, cereblon-dependent proinsulin degrader.Scientific reports · 2022Article
- Aberrant Splicing ofInternational journal of molecular sciences · 2022Article
- Novel Pathogenic De Novo INS p.T97P Variant Presenting With Severe Neonatal DKA.Endocrinology · 2022Article
- Genome Editing and Human Pluripotent Stem Cell Technologies for in vitro Monogenic Diabetes Modeling.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Review
- Genetic Etiology of Neonatal Diabetes Mellitus in Vietnamese Infants and Characteristics of Those WithFrontiers in endocrinology · 2022Article
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
- In celebration of a century with insulin - Update of insulin gene mutations in diabetes.Molecular metabolism · 2021Review
- Biological activity versus physiological function of proinsulin C-peptide.Cellular and molecular life sciences : CMLS · 2021Article
- Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.The Journal of clinical investigation · 2021Review
- 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
- A Novel NonsenseFrontiers in endocrinology · 2021Article
- Structural Lessons From the Mutant Proinsulin Syndrome.Frontiers in endocrinology · 2021Review
2 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 1 institution in 1 country.
Funding
Abstract
Mutations in the preproinsulin protein that affect processing of preproinsulin to proinsulin or lead to misfolding of proinsulin are associated with diabetes. We examined the subcellular localization and secretion of 13 neonatal diabetes-associated human proinsulin proteins (A24D, G32R, G32S, L35P, C43G, G47V, F48C, G84R, R89C, G90C, C96Y, S101C and Y108C) in rat INS-1 insulinoma cells. These mutant proinsulin proteins accumulate in the endoplasmic reticulum (ER) and are poorly secreted except for G84R and in contrast to wild-type and hyperproinsulinemia-associated mutant proteins (H34D and R89H) which were sorted to secretory granules and efficiently secreted. We also examined the effect of C96Y mutant proinsulin on the synthesis and secretion of wild-type insulin and observed a dominant-negative effect of the mutant proinsulin on the synthesis and secretion of wild-type insulin due to induction of the unfolded protein response and resulting attenuation of overall translation.
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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.