ArticleProceedings of the National Academy of Sciences of the United States of America2001
Defective trafficking and function of KATP channels caused by a sulfonylurea receptor 1 mutation associated with persistent hyperinsulinemic hypoglycemia of infancy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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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
65 citing papers in PubMed, 165 citations in OpenAlex.
- Identification and rescue of congenital hyperinsulinism-associated ABCC8 mutations that impair KThe Journal of biological chemistry · 2025Article
- Tyrosine phosphorylation of Kir6.2 subunit negatively regulates cardiac KBasic research in cardiology · 2025Article
- Article
- KFrontiers in endocrinology · 2023Review
- The reversible effects of free fatty acids on sulfonylurea-stimulated insulin secretion are related to the expression and dynamin-mediated endocytosis of KATP channels in pancreatic β cells.Endocrine connections · 2023Article
- 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
- Sulfonylurea Receptor 1 in Central Nervous System Injury: An Updated Review.International journal of molecular sciences · 2021Review
- Beta-Cell Ion Channels and Their Role in Regulating Insulin Secretion.Comprehensive Physiology · 2021Review
- Production and purification of ATP-sensitive potassium channel particles for cryo-electron microscopy.Methods in enzymology · 2021Article
- Cellular and systemic mechanisms for glucose sensing and homeostasis.Pflugers Archiv : European journal of physiology · 2020Review
- Pharmacological chaperones of ATP-sensitive potassium channels: Mechanistic insight from cryoEM structures.Molecular and cellular endocrinology · 2020Review
- Congenital hyperinsulinism disorders: Genetic and clinical characteristics.American journal of medical genetics. Part C, Seminars in medical genetics · 2019Review
- Novel dominant KAmerican journal of medical genetics. Part A · 2019Article
- Hyperinsulinaemic hypoglycaemia-an overview of a complex clinical condition.European journal of pediatrics · 2019Review
- Rab8a is involved in membrane trafficking of Kir6.2 in the MIN6 insulinoma cell line.Pflugers Archiv : European journal of physiology · 2019Article
- The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism.Frontiers in endocrinology · 2019Review
- Cryo-electron microscopy structures and progress toward a dynamic understanding of KThe Journal of general physiology · 2018Review
- Pharmacoperones as Novel Therapeutics for Diverse Protein Conformational Diseases.Physiological reviews · 2018Review
- Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations.The Journal of biological chemistry · 2016Article
- Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes.Endocrine reviews · 2016Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The ATP-sensitive potassium channel (K(ATP)) regulates insulin secretion in pancreatic beta cells. Loss of functional K(ATP) channels because of mutations in either the SUR1 or Kir6.2 channel subunit causes persistent hyperinsulinemic hypoglycemia of infancy (PHHI). We investigated the molecular mechanism by which a single phenylalanine deletion in SUR1 (DeltaF1388) causes PHHI. Previous studies have shown that coexpression of DeltaF1388 SUR1 with Kir6.2 results in no channel activity. We demonstrate here that the lack of functional expression is due to failure of the mutant channel to traffic to the cell surface. Trafficking of K(ATP) channels requires that the endoplasmic reticulum-retention signal, RKR, present in both SUR1 and Kir6.2, be shielded during channel assembly. To ask whether DeltaF1388 SUR1 forms functional channels with Kir6.2, we inactivated the RKR signal in DeltaF1388 SUR1 by mutation to AAA (DeltaF1388 SUR1(AAA)). Inactivation of similar endoplasmic reticulum-retention signals in the cystic fibrosis transmembrane conductance regulator has been shown to partially overcome the trafficking defect of a cystic fibrosis transmembrane conductance regulator mutation, DeltaF508. We found that coexpression of DeltaF1388 SUR1(AAA) with Kir6.2 led to partial surface expression of the mutant channel. Moreover, mutant channels were active. Compared with wild-type channels, the mutant channels have reduced ATP sensitivity and do not respond to stimulation by MgADP or diazoxide. The RKR --> AAA mutation alone has no effect on channel properties. Our results establish defective trafficking of K(ATP) channels as a molecular basis of PHHI and show that F1388 in SUR1 is critical for normal trafficking and function of K(ATP) channels.
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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.