title: Improvement of oral contraceptive-induced glucose dysregulation and dyslipidemia by valproic acid is independent of circulating corticosterone.
abstract: BACKGROUND
  Cardiometabolic disorders are rapidly becoming major public health challenges. Valproic acid (VPA) is a widely prescribed anticonvulsant drug.
  
  
  OBJECTIVE
  We hypothesized that treatment with VPA would improve the regulation of glucose and atherogenic dyslipidemia through reduction in circulating corticosterone.
  
  
  METHODS
  Female Wistar rats recieved (p.o.) combined oral contraceptive (COC) containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and valproic acid (VPA; 20 mg) for 8 weeks.
  
  
  RESULTS
  Treatment with COC led to elevated fasting blood glucose, insulin, corticosterone, triglycerides (TG), TG/HDL-cholesterol ratio, insulin resistance (IR) and impaired glucose tolerance. VPA significantly attenuated the alterations induced by COC treatment, but did not affect the corticosterone level. However, VPA treatment led to significant increases in plasma insulin, corticosterone, atherogenic lipids and impaired glucose tolerance in rats not treated with COC.
  
  
  CONCLUSIONS
  The findings in this study suggest that VPA mitigates against the development of COC-induced insulin resistance and dyslipidemia independent of elevated circulating corticosterone.
authors: a Cardiovascular and Molecular Physiology Unit, Department of Physiology, College of Health Sciences University of Ilorin , Ilorin , Nigeria .|b Cardiovascular Research Institute, Kyungpook National University School of Medicine , Daegu , Republic of Korea , and.
authors: Lawrence A
authors: LA
authors: Olatunji
authors: a Cardiovascular and Molecular Physiology Unit, Department of Physiology, College of Health Sciences University of Ilorin , Ilorin , Nigeria .
authors: Tolulope E
authors: TE
authors: Omolekulo
authors: a Cardiovascular and Molecular Physiology Unit, Department of Physiology, College of Health Sciences University of Ilorin , Ilorin , Nigeria .
authors: Taofeek O
authors: TO
authors: Usman
authors: b Cardiovascular Research Institute, Kyungpook National University School of Medicine , Daegu , Republic of Korea , and.|c Department of Pharmacology , Kyungpook National University School of Medicine , Daegu , Republic of Korea.
authors: InKyeom
authors: I
authors: Kim
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003277:Contraceptives, Oral, Combined / Q000633:toxicity*; D003345:Corticosterone / Q000097:blood*; D050171:Dyslipidemias / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D018149:Glucose Intolerance / Q000139:chemically induced / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D003277:Contraceptives, Oral, Combined; D014635:Valproic Acid; D003345:Corticosterone
keywords: Atherogenic lipids; HDACi; corticosterone; insulin resistance; oral contraceptive