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The anodal\/cathodal biphasic stimulation (ACBPS) electrical waveform resulted in a voltage\u2010 and stimulation duration\u2010dependent increase in insulin release. ACBPS elicited insulin release both in the presence and absence of glucose. Basal and ACBPS\u2010induced insulin secretion could be inhibited by mitochondrial poisons and calcium channel blockers, indicating that insulin release was dependent on adenosine triphosphate (ATP) and the influx of calcium. ACBPS parameters that released insulin caused no detectable plasma membrane damage or cytotoxicity, although temporary morphological changes could be observed immediately after ACBPS. ACBPS did not alter the plasma membrane transmembrane potential but did cause pronounced uptake of MitoTracker Red into the mitochondrial membrane, indicating an increased mitochondrial membrane potential. While the ATP:ADP ratio after ACBPS did not change, the guanosine triphosphate (GTP) levels increased and increased GTP levels have previously been associated with insulin release in INS\u20101 cells. These results provide evidence that ACBPS can have significant biological effects on cells. In the case of INS\u20101 cells, ACBPS promotes insulin release without causing cytotoxicity.<\/jats:p>","DOI":"10.1002\/jcp.28307","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T04:16:35Z","timestamp":1549944995000},"page":"16389-16399","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The effect of anodal\/cathodal biphasic electrical stimulation on insulin release"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5314-1622","authenticated-orcid":false,"given":"David","family":"Siegel","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Skaggs School of Pharmacy University of Colorado Anschutz Medical Campus Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serapio M.","family":"Baca","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Skaggs 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