ArticleProceedings of the National Academy of Sciences of the United States of America2007
Insulin gene mutations as a cause of permanent neonatal diabetes.
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 281 papers.
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Who cites it
281 citing papers in PubMed, 554 citations in OpenAlex.
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- Identification of the ACTB p.Ser348Leu de novo variant in individuals with syndromic neonatal diabetes.EBioMedicine · 2026Article
- METTL18 ensures pancreatic function by maintaining proper translation and proteostasis.Molecular metabolism · 2026Article
- A new form of diabetes caused by INS mutations defined by zygosity, stem cell and population data.EMBO molecular medicine · 2026Article
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- 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 and Clinical Profiles of Pediatric Monogenic Diabetes Subtypes: Comprehensive Genetic Analysis of 138 Patients.The Journal of clinical endocrinology and metabolism · 2025Article
- Monogenic diabetes: An evidence-based clinical approach.World journal of diabetes · 2025Review
- Renalase inhibition defends against acute and chronic β cell stress by regulating cell metabolism.Molecular metabolism · 2025Article
- Neonatal and Syndromic Forms of Diabetes.Current diabetes reports · 2025Review
- TanGIBLE: A selective probe for evaluating hydrophobicity-exposed defective proteins in live cells.The Journal of cell biology · 2025Article
- A Unique Phenotype of Maturity-Onset Diabetes of the Young With a Novel Disease-Causing Insulin Gene Variant.JCEM case reports · 2025Article
- Genetic variant profiling of neonatal diabetes mellitus in Iranian patients: Unveiling 58 distinct variants in 14 genes.Journal of diabetes investigation · 2024Article
- Monogenic Defects of Beta Cell Function: From Clinical Suspicion to Genetic Diagnosis and Management of Rare Types of Diabetes.International journal of molecular sciences · 2024Review
- Molecular basis of TMED9 oligomerization and entrapment of misfolded protein cargo in the early secretory pathway.Science advances · 2024Article
- Transient diabetes mellitus with ABCC8 variant successfully treated with sulfonylurea: Two case reports and review of literature.World journal of diabetes · 2024Article
- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
- Bax Inhibitor-1 preserves pancreatic β-cell proteostasis by limiting proinsulin misfolding and programmed cell death.Cell death & disease · 2024Article
221 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 2 institutions in 2 countries.
Funding
Abstract
We report 10 heterozygous mutations in the human insulin gene in 16 probands with neonatal diabetes. A combination of linkage and a candidate gene approach in a family with four diabetic members led to the identification of the initial INS gene mutation. The mutations are inherited in an autosomal dominant manner in this and two other small families whereas the mutations in the other 13 patients are de novo. Diabetes presented in probands at a median age of 9 weeks, usually with diabetic ketoacidosis or marked hyperglycemia, was not associated with beta cell autoantibodies, and was treated from diagnosis with insulin. The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin secretory pathway. The abnormally folded proinsulin molecule may induce the unfolded protein response and undergo degradation in the endoplasmic reticulum, leading to severe endoplasmic reticulum stress and potentially beta cell death by apoptosis. This process has been described in both the Akita and Munich mouse models that have dominant-acting missense mutations in the Ins2 gene, leading to loss of beta cell function and mass. One of the human mutations we report here is identical to that in the Akita mouse. The identification of insulin mutations as a cause of neonatal diabetes will facilitate the diagnosis and possibly, in time, treatment of this disorder.
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