ArticleThe Journal of clinical endocrinology and metabolism2010
Neonatal diabetes caused by mutations in sulfonylurea receptor 1: interplay between expression and Mg-nucleotide gating defects of ATP-sensitive potassium channels.
Article in The Journal of clinical endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- The Mutation Spectrum of Rare Variants in the Gene of Adenosine Triphosphate (ATP)-Binding Cassette Subfamily C Member 8 in Patients with a MODY Phenotype in Western Siberia.Journal of personalized medicine · 2023Article
- A Cantú syndrome mutation produces dual effects on KATP channels by disrupting ankyrin B regulation.The Journal of general physiology · 2023Article
- KFrontiers in endocrinology · 2023Review
- Subcellular trafficking and endocytic recycling of KAmerican journal of physiology. Cell physiology · 2022Review
- Channelopathy Genes in Pulmonary Arterial Hypertension.Biomolecules · 2022Review
- Role of Actionable Genes in Pursuing a True Approach of Precision Medicine in Monogenic Diabetes.Genes · 2022Review
- New insights into KNature reviews. Endocrinology · 2020Review
- Novel dominant KAmerican journal of medical genetics. Part A · 2019Article
- Functional characterization of activating mutations in the sulfonylurea receptor 1 (ABCC8) causing neonatal diabetes mellitus in Asian Indian children.Pediatric diabetes · 2019Article
- Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension.Circulation. Genomic and precision medicine · 2018Article
- KInternal medicine (Tokyo, Japan) · 2017Review
- Differential mechanisms of Cantú syndrome-associated gain of function mutations in the ABCC9 (SUR2) subunit of the KATP channel.The Journal of general physiology · 2015Article
- Structurally distinct ligands rescue biogenesis defects of the KATP channel complex via a converging mechanism.The Journal of biological chemistry · 2015Article
- Carbamazepine inhibits ATP-sensitive potassium channel activity by disrupting channel response to MgADP.Channels (Austin, Tex.) · 2014Article
- Pharmacological rescue of trafficking-impaired ATP-sensitive potassium channels.Frontiers in physiology · 2013Review
- Neonatal diabetes caused by activating mutations in the sulphonylurea receptor.Diabetes & metabolism journal · 2013Article
- Channeling dysglycemia: ion-channel variations perturbing glucose homeostasis.Trends in endocrinology and metabolism: TEM · 2012Review
- Mechanism of KATP hyperactivity and sulfonylurea tolerance due to a diabetogenic mutation in L0 helix of sulfonylurea receptor 1 (ABCC8).FEBS letters · 2011Article
- Current understanding of K ATP channels in neonatal diseases: focus on insulin secretion disorders.Acta pharmacologica Sinica · 2011Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
contextATP-sensitive potassium (KATP) channels regulate insulin secretion by coupling glucose metabolism to β-cell membrane potential. Gain-of-function mutations in the sulfonylurea receptor 1 (SUR1) or Kir6.2 channel subunit underlie neonatal diabetes.
objectiveThe objective of the study was to determine the mechanisms by which two SUR1 mutations, E208K and V324M, associated with transient neonatal diabetes affect KATP channel function.
designE208K or V324M mutant SUR1 was coexpressed with Kir6.2 in COS cells, and expression and gating properties of the resulting channels were assessed biochemically and electrophysiologically.
resultsBoth E208K and V324M augment channel response to MgADP stimulation without altering sensitivity to ATP4- or sulfonylureas. Surprisingly, whereas E208K causes only a small increase in MgADP response consistent with the mild transient diabetes phenotype, V324M causes a severe activating gating defect. Unlike E208K, V324M also impairs channel expression at the cell surface, which is expected to dampen its functional impact on β-cells. When either mutation was combined with a mutation in the second nucleotide binding domain of SUR1 previously shown to abolish Mg-nucleotide response, the activating effect of E208K and V324M was also abolished. Moreover, combination of E208K and V324M results in channels with Mg-nucleotide sensitivity greater than that seen in individual mutations alone.
conclusionThe results demonstrate that E208K and V324M, located in distinct domains of SUR1, enhance transduction of Mg-nucleotide stimulation from the SUR1 nucleotide binding folds to Kir6.2. Furthermore, they suggest that diabetes severity is determined by interplay between effects of a mutation on channel expression and channel gating.
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