{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:39:06Z","timestamp":1792525146572,"version":"4.5.0"},"reference-count":80,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>The cardiac isoform of phosphofructokinase-2\/fructose 2,6-biphosphatase (PFKFB2) is the heart\u2019s strongest glycolytic regulator but is degraded in the absence of insulin signaling. This makes PFKFB2 loss critical to understand in metabolic heart disease, of which impaired insulin signaling is a hallmark. Prolongation of the QT interval, risk of arrhythmia, and sudden cardiac death are also augmented in metabolic heart disease, raising a question as to whether crosstalk between glycolytic dysregulation and electrophysiological dysfunction exists.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We therefore assessed the impact of PFKFB2 loss on cardiac electrophysiology using a cardiomyocyte-specific PFKFB2 knockout mouse model (cKO) and litter-matched controls. To do so, we employed electrocardiography in the fed state and following 12 hours of fasting, examining physiology both at baseline and in the presence of an acute stimulant stress. To further investigate the arrhythmia mechanism, we used patch-clamp electrophysiology and IonOptix Ca\n                      <jats:sup>2+<\/jats:sup>\n                      transient measurements in ventricular cardiomyocytes isolated from control and cKO hearts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      The hearts of cKO mice exhibited prolonged repolarization, marked by QT and action potential duration prolongations. This occurred with impaired Ca\n                      <jats:sup>2+<\/jats:sup>\n                      reuptake and increased spontaneous Ca\n                      <jats:sup>2+<\/jats:sup>\n                      release events in ventricular cardiomyocytes. The latter were upregulated via O-GlcNAcylation, a post-translational modification enhanced in the fed state in cKO hearts. Ultimately, these changes culminated in ventricular tachyarrhythmia in cKO mice, which was enhanced in the fed relative to the fasted state.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These data suggest that in the presence of sufficient glucose availability, cardiac glycolytic dysregulation at the phosphofructokinase nexus is sufficient to promote cardiac electrophysiological instability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circep.126.014860","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:00:14Z","timestamp":1790154014000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["PFKFB2 Gates a Relationship Between Cardiac Glycolytic Regulation and Electrophysiological Function"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8421-6268","authenticated-orcid":true,"given":"Kylene M.","family":"Harold","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Physiology, University of Oklahoma Health Campus (K.M. 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