Kv2.1 Ablation Alters Glucose-Induced Islet Electrical Activity, Enhancing Insulin Secretion
Open accessAbstract
Voltage-gated potassium currents (Kv), primarily due to Kv2.1 channels, are activated by glucose-stimulated pancreatic beta cell depolarization, but the exact role (or roles) of this channel in regulating insulin secretion remains uncertain. Here we report that, compared with controls, Kv2.1 null mice have reduced fasting blood glucose levels and elevated serum insulin levels. Glucose tolerance is improved and insulin secretion is enhanced compared to control animals, with similar results in isolated islets in vitro. Isolated Kv2.1(-/-) beta cells have residual Kv currents, which are decreased by 83% at +50 mV compared with control cells. The glucose-induced action potential (AP) duration is increased while the firing frequency is diminished, similar to the effect of specific toxins on control cells but substantially different from the effect of the less specific blocker tetraethylammonium. These results reveal the specific role of Kv2.1 in modulating glucose-stimulated APs of beta cells, exposing additional important currents involved in regulating physiological insulin secretion.
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Experiments on Kcnb1-deficient mice make it clear that Kv2.1 channels account for most of the delayed outward current in mouse β-cells.
“However, experiments on Kcnb1-deficient mice make it clear that these channels account for most of the delayed outward current in mouse β-cells (310).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [310]
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- [1]1. Ahn, J.E. ∙ Byun, J.H. ∙ Ko, M.S. ... Case report: neuroendocrine carcinoma of the gallbladder causing hyperinsulinaemic hypoglycaemia Clin. Radiol. 2007; 62:391-394 Full Text Full Text (PDF) Scopus (13) PubMed Google Scholar
- [2]2. Ashcroft, F.M. ∙ Rorsman, P. Electrophysiology of the pancreatic beta-cell Prog. Biophys. Mol. Biol. 1989; 54:87-143 Crossref Scopus (1000) PubMed Google Scholar
- [3]3. Atwater, I. ∙ Ribalet, B. ∙ Rojas, E. Mouse pancreatic beta-cells: tetraethylammonium blockage of the potassium permeability increase induced by depolarization J. Physiol. 1979; 288:561-574 PubMed Google Scholar
- [4]4. Beigelman, P.M. ∙ Thomas, L.J. ∙ Shu, M.J. ... Insulin from individual isolated islets of Langerhans 2. Effect of glucose in varying concentrations J. Physiol. (Paris). 1976; 72:721-728 PubMed Google Scholar
- [5]5. Betsholtz, C. ∙ Baumann, A. ∙ Kenna, S. ... Expression of voltage-gated K+ channels in insulin-producing cells. Analysis by polymerase chain reaction FEBS Lett. 1990; 263:121-126 Crossref Scopus (34) PubMed Google Scholar
- [6]6. Bokvist, K. ∙ Rorsman, P. ∙ Smith, P.A. Effects of external tetraethylammonium ions and quinine on delayed rectifying K+ channels in mouse pancreatic beta-cells J. Physiol. 1990; 423:311-325 Crossref Scopus (62) PubMed Google Scholar
- [7]7. Dean, P.M. ∙ Matthews, E.K. Glucose-induced electrical activity in pancreatic islet cells J. Physiol. 1970; 210:255-264 Crossref Scopus (264) PubMed Google Scholar
- [8]8. Dukes, I.D. ∙ Philipson, L.H. K+ channels: generating excitement in pancreatic beta-cells Diabetes. 1996; 45:845-853 Crossref PubMed Google Scholar
- [9]9. Escoubas, P. ∙ Diochot, S. ∙ Celerier, M.L. ... Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies Mol. Pharmacol. 2002; 62:48-57 Crossref Scopus (156) PubMed Google Scholar
- [10]10. Gopel, S.O. ∙ Kanno, T. ∙ Barg, S. ... Patch-clamp characterisation of somatostatin-secreting -cells in intact mouse pancreatic islets J. Physiol. 2000; 528:497-507 Crossref Scopus (131) PubMed Google Scholar
- [11]11. Henquin, J.C. Tetraethylammonium potentiation of insulin release and inhibition of rubidium efflux in pancreatic islets Biochem. Biophys. Res. Commun. 1977; 77:551-556 Crossref Scopus (47) PubMed Google Scholar
- [12]12. Herrington, J. Gating modifier peptides as probes of pancreatic beta-cell physiology Toxicon. 2007; 49:231-238 Crossref Scopus (43) PubMed Google Scholar
- [13]13. Herrington, J. ∙ Sanchez, M. ∙ Wunderler, D. ... Biophysical and pharmacological properties of the voltage-gated potassium current of human pancreatic beta-cells J. Physiol. 2005; 567:159-175 Crossref Scopus (37) PubMed Google Scholar
- [14]14. Herrington, J. ∙ Zhou, Y.P. ∙ Bugianesi, R.M. ... Blockers of the delayed-rectifier potassium current in pancreatic beta-cells enhance glucose-dependent insulin secretion Diabetes. 2006; 55:1034-1042 Crossref Scopus (141) PubMed Google Scholar
- [15]15. Houamed, K. ∙ Fu, J. ∙ Roe, M.W. ... Electrophysiology of the pancreatic beta cell LeRoith, D. ∙ Taylor, S.I. ∙ Olefsky, J.M. (Editors) Diabetes Mellitus Lippincott Williams and Wilkins, Philadelphia, 2004; 51-68 Google Scholar
- [16]16. Kirsch, G.E. ∙ Drewe, J.A. Gating-dependent mechanism of 4-aminopyridine block in two related potassium channels J. Gen. Physiol. 1993; 102:797-816 Crossref Scopus (94) PubMed Google Scholar
- [17]17. Kukuljan, M. ∙ Goncalves, A.A. ∙ Atwater, I. Charybdotoxin-sensitive K(Ca) channel is not involved in glucose-induced electrical activity in pancreatic beta-cells J. Membr. Biol. 1991; 119:187-195 Crossref Scopus (56) PubMed Google Scholar
- [18]18. MacDonald, P.E. ∙ Ha, X.F. ∙ Wang, J. ... Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion Mol. Endocrinol. 2001; 15:1423-1435 Crossref Scopus (168) PubMed Google Scholar
- [19]19. MacDonald, P.E. ∙ Sewing, S. ∙ Wang, J. ... Inhibition of Kv2.1 voltage-dependent K+ channels in pancreatic beta-cells enhances glucose-dependent insulin secretion J. Biol. Chem. 2002; 277:44938-44945 Crossref Scopus (156) PubMed Google Scholar
- [20]20. MacDonald, P.E. ∙ Wang, G. ∙ Tsuk, S. ... Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K(+) channels in neuroendocrine islet beta-cells through an interaction with the channel N terminus Mol. Endocrinol. 2002; 16:2452-2461 Crossref Scopus (72) PubMed Google Scholar
- [21]21. Nestorowicz, A. ∙ Wilson, B.A. ∙ Schoor, K.P. ... Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews Hum. Mol. Genet. 1996; 5:1813-1822 Crossref Scopus (246) PubMed Google Scholar
- [22]22. Philipson, L.H. Beta-cell ion channels: keys to endodermal excitability Horm. Metab. Res. 1999; 31:455-461 Crossref Scopus (25) PubMed Google Scholar
- [23]23. Philipson, L.H. ∙ Rosenberg, M.P. ∙ Kuznetsov, A. ... Delayed rectifier K+ channel overexpression in transgenic islets and beta-cells associated with impaired glucose responsiveness J. Biol. Chem. 1994; 269:27787-27790
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
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Baver, S. B., Hope, K., Guyot, S., Bjørbaek, C., Kaczorowski, C., & O'Connell, K. M. S. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.4861-12.2014 · Cited by 203 · see citing works
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- Authors
- Jacobson, D. A., Kuznetsov, A., Lopez, J. P., Kash, S., Ämmälä, C. E., & Philipson, L. H.
- Affiliations
- University of Chicago (US)
- Deltagen (United States) (US)
- GlaxoSmithKline (United States) (US)
- Corresponding author
- Jacobson, David A.
- Philipson, Louis H.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 6
- Issue
- 3
- Pages
- 229-235
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2699758
- OpenAlex
- W2071651200
- Cited by
- 180
- References
- 0
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 13 · 2023: 2 · 2022: 8 · 2021: 17 · 2020: 7 · 2019: 14 · 2018: 9 · 2017: 18 · 2016: 5 · 2015: 10 · 2014: 15 · 2013: 9 · 2012: 10
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK048494, DK 20595, DK-48494, P60DK020595, P30DK020595)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- Kv2.1 potassium channel, voltage-gated potassium currents, pancreatic beta cells, insulin secretion, glucose tolerance, tetraethylammonium
- MeSH terms
- Animals, Calcium, Female, Glucose, Homeostasis, Humans, Insulin, Islets of Langerhans, Membrane Potentials, Mice, Inbred C57BL, Mice, Knockout, Patch-Clamp Techniques, Mice, Shab Potassium Channels
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