ArticleDiabetes2013
Molecular mechanism of sulphonylurea block of K(ATP) channels carrying mutations that impair ATP inhibition and cause neonatal diabetes.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Low-Dose Sulfonylurea Plus DPP4 Inhibitor Lower Blood Glucose and Enhance Beta-Cell Function Without Hypoglycemia.The Journal of clinical endocrinology and metabolism · 2024Trial
- Review
- Light-stimulated insulin secretion from pancreatic islet-like organoids derived from human pluripotent stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Metabolic Messengers: glucagon.Nature metabolism · 2023Review
- Personalized Therapeutics for KAnnual review of pharmacology and toxicology · 2023Review
- Mechanistic insights on KATP channel regulation from cryo-EM structures.The Journal of general physiology · 2023Review
- Article
- Sulfonylureas in the Current Practice of Type 2 Diabetes Management: Are They All the Same? Consensus from the Gulf Cooperation Council (GCC) Countries Advisory Board on Sulfonylureas.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2021Article
- Review
- Clinical features and partial proportional molecular genetics in neonatal diabetes mellitus: a retrospective analysis in southwestern China.Endocrine · 2020Article
- New insights into KNature reviews. Endocrinology · 2020Review
- Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1.Obesity (Silver Spring, Md.) · 2019Article
- Ion Transporters, Channelopathies, and Glucose Disorders.International journal of molecular sciences · 2019Review
- ATP binding without hydrolysis switches sulfonylurea receptor 1 (SUR1) to outward-facing conformations that activate KThe Journal of biological chemistry · 2019Article
- Role of the C-terminus of SUR in the differential regulation of β-cell and cardiac KThe Journal of physiology · 2018Article
- A novel high-affinity inhibitor against the human ATP-sensitive Kir6.2 channel.The Journal of general physiology · 2018Article
- Article
- Conserved functional consequences of disease-associated mutations in the slide helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive potassium channel.The Journal of biological chemistry · 2017Article
- KInternal medicine (Tokyo, Japan) · 2017Review
- Neonatal Diabetes and the KTrends in endocrinology and metabolism: TEM · 2017Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Sulphonylurea drugs are the therapy of choice for treating neonatal diabetes (ND) caused by mutations in the ATP-sensitive K(+) channel (KATP channel). We investigated the interactions between MgATP, MgADP, and the sulphonylurea gliclazide with KATP channels expressed in Xenopus oocytes. In the absence of MgATP, gliclazide block was similar for wild-type channels and those carrying the Kir6.2 ND mutations R210C, G334D, I296L, and V59M. Gliclazide abolished the stimulatory effect of MgATP on all channels. Conversely, high MgATP concentrations reduced the gliclazide concentration, producing a half-maximal block of G334D and R201C channels and suggesting a mutual antagonism between nucleotide and gliclazide binding. The maximal extent of high-affinity gliclazide block of wild-type channels was increased by MgATP, but this effect was smaller for ND channels; channels that were least sensitive to ATP inhibition showed the smallest increase in sulphonylurea block. Consequently, G334D and I296L channels were not fully blocked, even at physiological MgATP concentrations (1 mmol/L). Glibenclamide block was also reduced in β-cells expressing Kir6.2-V59M channels. These data help to explain why patients with some mutations (e.g., G334D, I296L) are insensitive to sulphonylurea therapy, why higher drug concentrations are needed to treat ND than type 2 diabetes, and why patients with severe ND mutations are less prone to drug-induced hypoglycemia.
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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.