ArticleDiabetes2007
Congenital hyperinsulinism associated ABCC8 mutations that cause defective trafficking of ATP-sensitive K+ channels: identification and rescue.
Article in Diabetes, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 113 citations in OpenAlex.
- Digenic HNF1A and ABCC8 variants provide mechanistic insight into early-onset diabetes.The Journal of clinical endocrinology and metabolism · 2026Article
- Congenital Hyperinsulinism With Paternally InheritedJournal of the ASEAN Federation of Endocrine Societies · 2026Article
- Diazoxide-Responsive Congenital Hyperinsulinism in a Preterm Infant With HomozygousCase reports in endocrinology · 2026Article
- Structural insights into toxicant export mediated by ABCC2 in Arabidopsis thaliana.Nature communications · 2025Article
- Identification and rescue of congenital hyperinsulinism-associated ABCC8 mutations that impair KThe Journal of biological chemistry · 2025Article
- Genetic and clinical insights into acute kidney injury in maturity-onset diabetes of the young caused by theExperimental and therapeutic medicine · 2025Article
- Automated patch clamp analysis of heterologously expressed Kir6.2/SUR1 and Kir6.1/SUR2B KAmerican journal of physiology. Cell physiology · 2025Article
- Article
- Select Endocrine Disorders and Exosomes in Early PDAC Diagnosis.International journal of molecular sciences · 2024Review
- The Elusive Nature of ABCC8-related Maturity-Onset Diabetes of the Young (ABCC8-MODY). A Review of the Literature and Case Discussion.Current diabetes reports · 2024Review
- A loss-of-function mutation in KCNJ11 causing sulfonylurea-sensitive diabetes in early adult life.Diabetologia · 2024Article
- Noninsulinoma Pancreatogenous Hypoglycemia Syndrome in a Patient With 1p36 Deletion Syndrome.JCEM case reports · 2024Article
- Non-radioactive RbMethods in molecular biology (Clifton, N.J.) · 2024Article
- KFrontiers in endocrinology · 2023Review
- Maturity-Onset Diabetes of the Young: Mutations, Physiological Consequences, and Treatment Options.Journal of personalized medicine · 2022Review
- The dynamic interplay of PIPThe Journal of physiology · 2022Article
- Localized islet nuclear enlargement hyperinsulinism (LINE-HI) due to ABCC8 and GCK mosaic mutations.European journal of endocrinology · 2022Article
- Carbamazepine promotes surface expression of mutant Kir6.2-A28V ATP-sensitive potassium channels by modulating Golgi retention and autophagy.The Journal of biological chemistry · 2022Article
- Photo-Switchable Sulfonylureas Binding to ATP-Sensitive Potassium Channel Reveal the Mechanism of Light-Controlled Insulin Release.The journal of physical chemistry. B · 2021Article
- Structure of Ycf1p reveals the transmembrane domain TMD0 and the regulatory region of ABCC transporters.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Congenital hyperinsulinism (CHI) is a disease characterized by persistent insulin secretion despite severe hypoglycemia. Mutations in the pancreatic ATP-sensitive K(+) (K(ATP)) channel proteins sulfonylurea receptor 1 (SUR1) and Kir6.2, encoded by ABCC8 and KCNJ11, respectively, is the most common cause of the disease. Many mutations in SUR1 render the channel unable to traffic to the cell surface, thereby reducing channel function. Previous studies have shown that for some SUR1 trafficking mutants, the defects could be corrected by treating cells with sulfonylureas or diazoxide. The purpose of this study is to identify additional mutations that cause channel biogenesis/trafficking defects and those that are amenable to rescue by pharmacological chaperones. Fifteen previously uncharacterized CHI-associated missense SUR1 mutations were examined for their biogenesis/trafficking defects and responses to pharmacological chaperones, using a combination of immunological and functional assays. Twelve of the 15 mutations analyzed cause reduction in cell surface expression of K(ATP) channels by >50%. Sulfonylureas rescued a subset of the trafficking mutants. By contrast, diazoxide failed to rescue any of the mutants. Strikingly, the mutations rescued by sulfonylureas are all located in the first transmembrane domain of SUR1, designated as TMD0. All TMD0 mutants rescued to the cell surface by the sulfonylurea tolbutamide could be subsequently activated by metabolic inhibition on tolbutamide removal. Our study identifies a group of CHI-causing SUR1 mutations for which the resulting K(ATP) channel trafficking and expression defects may be corrected pharmacologically to restore channel function.
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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.