{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T16:30:10Z","timestamp":1781541010657,"version":"3.54.5"},"reference-count":32,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2014,3,15]]},"abstract":"<jats:p> The question whether K<jats:sup>+<\/jats:sup> depolarization is an appropriate experimental substitute for the physiological nutrient-induced depolarization of the \u03b2-cell plasma membrane was investigated using primary mouse \u03b2-cells and islets. At basal glucose 40 mM K<jats:sup>+<\/jats:sup> induced a massive monophasic response, whereas 15 mM K<jats:sup>+<\/jats:sup> had only a minimal insulinotropic effect, even though the increase in the cytosolic Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) was not inferior to that by 20 mM glucose. In voltage-clamp experiments, Ca<jats:sup>2+<\/jats:sup> influx appeared as nifedipine-inhibitable inward action currents in the presence of sulfonylurea plus TEA to block compensatory outward K<jats:sup>+<\/jats:sup> currents. Under these conditions, 15 mM K<jats:sup>+<\/jats:sup> induced prolonged action currents and 40 mM K<jats:sup>+<\/jats:sup> transformed the action current pattern into a continuous inward current. Correspondingly, 15 mM K<jats:sup>+<\/jats:sup> led to an oscillatory increase and 40 mM K<jats:sup>+<\/jats:sup> to a plateau of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> superimposed on the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> elevated by sulfonylurea plus TEA. Raising K<jats:sup>+<\/jats:sup> to 15 or 40 mM in the presence of sulfonylurea (\u00b1TEA) led to a fast further increase of insulin secretion. This was reduced to basal levels by nifedipine or CoCl<jats:sub>2<\/jats:sub>. The effects of 15 mM K<jats:sup>+<\/jats:sup> on depolarization, action currents, and insulin secretion were mimicked by adding 35 mM Cs<jats:sup>+<\/jats:sup> and those of 40 mM K<jats:sup>+<\/jats:sup> by adding 35 mM Rb<jats:sup>+<\/jats:sup>, in parallel with their ability to substitute for K<jats:sup>+<\/jats:sup> as permeant cation. In conclusion, the alkali metals K<jats:sup>+<\/jats:sup>, Rb<jats:sup>+<\/jats:sup>, or Cs<jats:sup>+<\/jats:sup> concentration-dependently transform the pattern of Ca<jats:sup>2+<\/jats:sup> influx into the \u03b2-cell and may thus generate stimuli of supraphysiological strength for insulin secretion. <\/jats:p>","DOI":"10.1152\/ajpendo.00362.2013","type":"journal-article","created":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T04:44:38Z","timestamp":1390452278000},"page":"E697-E706","source":"Crossref","is-referenced-by-count":19,"title":["Insulinotropic effect of high potassium concentration beyond plasma membrane depolarization"],"prefix":"10.1152","volume":"306","author":[{"given":"M.","family":"Belz","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Braunschweig, Braunschweig, 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