ArticleDiabetologia2012
The voltage-dependent potassium channel subunit Kv2.1 regulates insulin secretion from rodent and human islets independently of its electrical function.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Ancestry-informative regulatory variants at KCNB1 modulate adipogenesis and body mass index.Frontiers in endocrinology · 2026Article
- Article
- KCNB1-Leptin receptor complexes couple electric and endocrine function in the melanocortin neurons of the hypothalamus.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Molecular mechanism responsible for sex differences in electrical activity of mouse pancreatic β cells.JCI insight · 2024Article
- KCNH6 channel promotes insulin exocytosis via interaction with Munc18-1 independent of electrophysiological processes.Cellular and molecular life sciences : CMLS · 2024Article
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive Physiology · 2023Article
- Regulation of neuronal excitation-transcription coupling by Kv2.1-induced clustering of somatic L-type CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- EVAP: A two-photon imaging tool to study conformational changes in endogenous Kv2 channels in live tissues.The Journal of general physiology · 2021Article
- Review
- A role for alternative splicing in circadian control of exocytosis and glucose homeostasis.Genes & development · 2020Article
- Recent Insights into Beta-cell Exocytosis in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Ion Channels of the Islets in Type 2 Diabetes.Journal of molecular biology · 2020Review
- A glucose-dependent spatial patterning of exocytosis in human β-cells is disrupted in type 2 diabetes.JCI insight · 2019Article
- Remodeling neuronal ER-PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels.Molecular biology of the cell · 2018Article
- KThe Journal of biological chemistry · 2018Article
- Kv2.1 Clustering Contributes to Insulin Exocytosis and Rescues Human β-Cell Dysfunction.Diabetes · 2017Article
- Kv5, Kv6, Kv8, and Kv9 subunits: No simple silent bystanders.The Journal of general physiology · 2016Review
- Synthesis and Biological Evaluation of New Tricyclic Dihydropyridine Based Derivatives on Potassium Channels.Iranian journal of pharmaceutical research : IJPR · 2016Article
- Pancreatic Beta Cell G-Protein Coupled Receptors and Second Messenger Interactions: A Systems Biology Computational Analysis.PloS one · 2016Article
- Synthesis of an azido-tagged low affinity ratiometric calcium sensor.Tetrahedron · 2015Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
aims/hypothesisIt is thought that the voltage-dependent potassium channel subunit Kv2.1 (Kv2.1) regulates insulin secretion by controlling beta cell electrical excitability. However, this role of Kv2.1 in human insulin secretion has been questioned. Interestingly, Kv2.1 can also regulate exocytosis through direct interaction of its C-terminus with the soluble NSF attachment receptor (SNARE) protein, syntaxin 1A. We hypothesised that this interaction mediates insulin secretion independently of Kv2.1 electrical function.
methodsWild-type Kv2.1 or mutants lacking electrical function and syntaxin 1A binding were studied in rodent and human beta cells, and in INS-1 cells. Small intracellular fragments of the channel were used to disrupt native Kv2.1-syntaxin 1A complexes. Single-cell exocytosis and ion channel currents were monitored by patch-clamp electrophysiology. Interaction between Kv2.1, syntaxin 1A and other SNARE proteins was probed by immunoprecipitation. Whole-islet Ca(2+)-responses were monitored by ratiometric Fura red fluorescence and insulin secretion was measured.
resultsUpregulation of Kv2.1 directly augmented beta cell exocytosis. This happened independently of channel electrical function, but was dependent on the Kv2.1 C-terminal syntaxin 1A-binding domain. Intracellular fragments of the Kv2.1 C-terminus disrupted native Kv2.1-syntaxin 1A interaction and impaired glucose-stimulated insulin secretion. This was not due to altered ion channel activity or impaired Ca(2+)-responses to glucose, but to reduced SNARE complex formation and Ca(2+)-dependent exocytosis. CONCLUSIONS/
interpretationDirect interaction between syntaxin 1A and the Kv2.1 C-terminus is required for efficient insulin exocytosis and glucose-stimulated insulin secretion. This demonstrates that native Kv2.1-syntaxin 1A interaction plays a key role in human insulin secretion, which is separate from the channel's electrical function.
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