ArticleDiabetologia2011
BK channels affect glucose homeostasis and cell viability of murine pancreatic beta cells.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 49 citations in OpenAlex.
- Investigation of Pancreatic-beta Cells Role in the Biological Process of Ageing.Endocrine, metabolic & immune disorders drug targets · 2024Review
- The Transcriptome and Epigenome Reveal Novel Changes in Transcription Regulation During Pancreatic Rat Islet Maturation.Endocrinology · 2021Article
- Neonatal Diabetes in Patients Affected by Liang-Wang Syndrome Carrying KCNMA1 Variant p.(Gly375Arg) Suggest a Potential Role of CaCurrent issues in molecular biology · 2021Article
- Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis.PLoS pathogens · 2021Article
- Regulatory effects of protein S-acylation on insulin secretion and insulin action.Open biology · 2021Review
- Characterization of Signaling Pathways Associated with Pancreatic β-cell Adaptive Flexibility in Compensation of Obesity-linked Diabetes inMolecular & cellular proteomics : MCP · 2020Article
- Possible New Strategies for the Treatment of Congenital Hyperinsulinism.Frontiers in endocrinology · 2020Article
- Lrrc55 is a novel prosurvival factor in pancreatic islets.American journal of physiology. Endocrinology and metabolism · 2019Article
- Review
- ATP mediates a negative autocrine signal on stimulus-secretion coupling in mouse pancreatic β-cells.Endocrine · 2019Article
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- Survival and growth of C57BL/6J mice lacking the BK channel,Physiological reports · 2017Article
- Gene expression signature predicts human islet integrity and transplant functionality in diabetic mice.PloS one · 2017Article
- A Critical Role for β-Catenin in Modulating Levels of Insulin Secretion from β-Cells by Regulating Actin Cytoskeleton and Insulin Vesicle Localization.The Journal of biological chemistry · 2016Article
- Using Drosophila to discover mechanisms underlying type 2 diabetes.Disease models & mechanisms · 2016Review
- Generation of Kcnma1fl-tdTomato, a conditional deletion of the BK channel α subunit in mouse.Physiological reports · 2015Article
- Imaging large cohorts of single ion channels and their activity.Frontiers in endocrinology · 2013Review
- Polyunsaturated Fatty Acids Modulate the Association between PIK3CA-KCNMB3 Genetic Variants and Insulin Resistance.PloS one · 2013Article
- Article
- The central role of calcium in the effects of cytokines on beta-cell function: implications for type 1 and type 2 diabetes.Cell calcium · 2011Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
aims/hypothesisEvidence is accumulating that Ca(2+)-regulated K(+) (K(Ca)) channels are important for beta cell function. We used BK channel knockout (BK-KO) mice to examine the role of these K(Ca) channels for glucose homeostasis, beta cell function and viability.
methodsGlucose and insulin tolerance were tested with male wild-type and BK-KO mice. BK channels were detected by single-cell RT-PCR, cytosolic Ca(2+) concentration ([Ca(2+)](c)) by fura-2 fluorescence, and insulin secretion by radioimmunoassay. Electrophysiology was performed with the patch-clamp technique. Apoptosis was detected via caspase 3 or TUNEL assay.
resultsBK channels were expressed in murine pancreatic beta cells. BK-KO mice were normoglycaemic but displayed markedly impaired glucose tolerance. Genetic or pharmacological deletion of the BK channel reduced glucose-induced insulin secretion from isolated islets. BK-KO and BK channel inhibition (with iberiotoxin, 100 nmol/l) broadened action potentials and abolished the after-hyperpolarisation in glucose-stimulated beta cells. However, BK-KO did not affect action potential frequency, the plateau potential at which action potentials start or glucose-induced elevation of [Ca(2+)](c). BK-KO had no direct influence on exocytosis. Importantly, in BK-KO islet cells the fraction of apoptotic cells and the rate of cell death induced by oxidative stress (H(2)O(2), 10-100 μmol/l) were significantly increased compared with wild-type controls. Similar effects were obtained with iberiotoxin. Determination of H(2)O(2)-induced K(+) currents revealed that BK channels contribute to the hyperpolarising K(+) current activated under conditions of oxidative stress. CONCLUSIONS/
interpretationAblation or inhibition of BK channels impairs glucose homeostasis and insulin secretion by interfering with beta cell stimulus-secretion coupling. In addition, BK channels are part of a defence mechanism against apoptosis and oxidative stress.
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