{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:00:05Z","timestamp":1791309605779,"version":"4.3.1"},"reference-count":36,"publisher":"American Diabetes Association","issue":"6","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,6,1]]},"abstract":"<jats:p>OBJECTIVE\u2014 To characterize the voltage-gated ion channels in human \u03b2-cells from nondiabetic donors and their role in glucose-stimulated insulin release.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014 Insulin release was measured from intact islets. Whole-cell patch-clamp experiments and measurements of cell capacitance were performed on isolated \u03b2-cells. The ion channel complement was determined by quantitative PCR.<\/jats:p>\n               <jats:p>RESULTS\u2014 Human \u03b2-cells express two types of voltage-gated K+ currents that flow through delayed rectifying (KV2.1\/2.2) and large-conductance Ca2+-activated K+ (BK) channels. Blockade of BK channels (using iberiotoxin) increased action potential amplitude and enhanced insulin secretion by 70%, whereas inhibition of KV2.1\/2.2 (with stromatoxin) was without stimulatory effect on electrical activity and secretion. Voltage-gated tetrodotoxin (TTX)-sensitive Na+ currents (NaV1.6\/1.7) contribute to the upstroke of action potentials. Inhibition of Na+ currents with TTX reduced glucose-stimulated (6\u201320 mmol\/l) insulin secretion by 55\u201370%. Human \u03b2-cells are equipped with L- (CaV1.3), P\/Q- (CaV2.1), and T- (CaV3.2), but not N- or R-type Ca2+ channels. Blockade of L-type channels abolished glucose-stimulated insulin release, while inhibition of T- and P\/Q-type Ca2+ channels reduced glucose-induced (6 mmol\/l) secretion by 60\u201370%. Membrane potential recordings suggest that L- and T-type Ca2+ channels participate in action potential generation. Blockade of P\/Q-type Ca2+ channels suppressed exocytosis (measured as an increase in cell capacitance) by &amp;gt;80%, whereas inhibition of L-type Ca2+ channels only had a minor effect.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014 Voltage-gated T-type and L-type Ca2+ channels as well as Na+ channels participate in glucose-stimulated electrical activity and insulin secretion. Ca2+-activated BK channels are required for rapid membrane repolarization. Exocytosis of insulin-containing granules is principally triggered by Ca2+ influx through P\/Q-type Ca2+ channels.<\/jats:p>","DOI":"10.2337\/db07-0991","type":"journal-article","created":{"date-parts":[[2008,4,5]],"date-time":"2008-04-05T00:59:28Z","timestamp":1207357168000},"page":"1618-1628","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":385,"title":["Voltage-Gated Ion Channels in Human Pancreatic \u03b2-Cells: Electrophysiological Characterization and Role in Insulin Secretion"],"prefix":"10.2337","volume":"57","author":[{"given":"Matthias","family":"Braun","sequence":"first","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reshma","family":"Ramracheya","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovita","family":"Karanauskaite","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Partridge","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Rorsman","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031303141505500_R1","doi-asserted-by":"crossref","unstructured":"Rorsman P: The pancreatic beta-cell as a fuel sensor: an electrophysiologist's viewpoint. 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