Carvedilol suppresses fatty acid oxidation and stimulates glycolysis in C2C12 cells

BEŞİKCİ A., Suzmecelik E., ÖZÇELİKAY A. T.

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, cilt.90, sa.8, ss.1087-1093, 2012 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 90 Sayı: 8
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1139/y2012-015
  • Dergi Adı: CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1087-1093
  • Anahtar Kelimeler: carvedilol, bisoprolol, beta-blockers, C2C12, fatty acid oxidation, glycolysis, CHRONIC HEART-FAILURE, ISOLATED RAT HEPATOCYTES, METOPROLOL EUROPEAN TRIAL, ACTIVATED PROTEIN-KINASE, SCALE CLINICAL-TRIALS, BETA-BLOCKERS, DIABETES-MELLITUS, DILATED CARDIOMYOPATHY, GLUCOSE-METABOLISM, INSULIN-RESISTANCE
  • Ankara Üniversitesi Adresli: Evet

Özet

Beta adrenergic receptor blocking drugs (beta-blockers) are used chronically in many cardiovascular diseases such as hypertension, ischemic heart disease, arrhythmia, and heart failure. Beneficial effects are associated with the inhibition of symphathetic nervous system hyperactivity, reduction of heart rate, and remodeling by blocking the mitogenic activity of catecholamines. A possible effect of b-blockers on substrate metabolism has also been suggested. The direct effects of beta-blockers on mouse C2C12 cells were investigated in this study. C2C12 cells were grown in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and differentiated into myotubes in the same medium that contained 1% FBS. Palmitic acid oxidation and glycolysis were measured by using [9,10-H-3] palmitate and [5-H-3] glucose, respectively. The amount of (H2O)-H-3 was measured as an indicator of substrate usage. Carvedilol (100 mu mol/L) inhibited palmitate oxidation and increased glycolysis by nearly 50%. Prazosin altered substrate metabolism in a similar fashion as carvedilol, whereas propranolol or bisoprolol were devoid of metabolic effects. When added to mimic sympathetic activation, epinephrine stimulated glycolysis but did not alter fatty acid oxidation. Based on these results, carvedilol appears to have direct effects on substrate metabolism that are related to the blockade of alpha 1 adrenergic receptors.