title: Glucagon-like peptide-1 regulates calcium homeostasis and electrophysiological activities of HL-1 cardiomyocytes.
abstract: Glucagon like-peptide-1 (GLP-1) is an incretin hormone with antidiabetic effects through stimulating insulin secretion, β cell neogenesis, satiety sensation, and inhibiting glucagon secretion. Administration of GLP-1 provides cardioprotective effects through attenuating cardiac inflammation and insulin resistance. GLP-1 also modulates the heart rate and systolic pressure, which suggests that GLP-1 may have cardiac electrical effects. Therefore, the purposes of this study were to evaluate whether GLP-1 has direct cardiac effects and identify the underlying mechanisms. Patch clamp, confocal microscopy with Fluo-3 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, calcium homeostasis, and calcium regulatory proteins in HL-1 atrial myocytes with and without GLP-1 (1 and 10nM) incubation for 24h. GLP-1 (1 and 10nM) and control cells had similar action potential durations. However, GLP-1 at 10nM significantly increased calcium transients and sarcoplasmic reticular Ca(2+) contents. Compared to the control, GLP-1 (10nM)-treated cells significantly decreased phosphorylation of the ryanodine receptor at S2814 and total phospholamban, but there were similar protein levels of sarcoplasmic reticular Ca(2+)-ATPase and the sodium-calcium exchanger. Moreover, exendin (9-39) amide (a GLP-1 receptor antagonist, 10nM) attenuated GLP-1-mediated effects on total SR content and phosphorylated ryanodine receptor S2814. This study demonstrates GLP-1 may regulate HL-1 cell arrhythmogenesis through modulating calcium handling proteins.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jen-Hung
authors.initials: JH
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Division of Endocrinology and Metabolism, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ting-I
authors.initials: TI
authors.lastname: Lee
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: yuhsunkao@gmail.com.
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.affiliation: Division of Cardiology and Cardiovascular Research Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tze-Fan
authors.initials: TF
authors.lastname: Chazo
authors.affiliation: Division of Cardiology and Cardiovascular Research Center, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University, School of Medicine, Taipei, Taiwan.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: a9900112@ms15.hinet.net.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000814:Aniline Compounds; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D017136:Ion Transport / Q000187:drug effects; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D061251:Primary Cell Culture; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism; D014966:Xanthenes; D000099211:Phospholamban
chemical_list: D000814:Aniline Compounds; D002110:Caffeine; D002118:Calcium; D002135:Calcium-Binding Proteins; D005456:Fluorescent Dyes; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D014966:Xanthenes; D000099211:Phospholamban; C000593834:Glp1r protein, mouse; C059715:Fluo-3; C083773:exendin (9-39)
keywords: Atrial arrhythmogenesis; Calcium handling protein; Glucagon like-peptide-1; Ryanodine receptor