Low-dose spironolactone ameliorates insulin resistance and suppresses elevated plasminogen activator inhibitor-1 during gestational testosterone exposure.

Autor: Olatunji LA; a Department of Physiology, Cardiovascular Research Laboratory , College of Health Sciences, University of Ilorin , Ilorin , Nigeria., Usman TO; a Department of Physiology, Cardiovascular Research Laboratory , College of Health Sciences, University of Ilorin , Ilorin , Nigeria.; b Department of Physiology, Cardiovascular Unit, College of Health sciences , Osun State University , Osogbo , Nigeria., Akinade AI; a Department of Physiology, Cardiovascular Research Laboratory , College of Health Sciences, University of Ilorin , Ilorin , Nigeria., Adeyanju OA; a Department of Physiology, Cardiovascular Research Laboratory , College of Health Sciences, University of Ilorin , Ilorin , Nigeria., Kim I; c Department of Pharmacology, Cardiovascular Research Institute , Kyungpook National University School of Medicine , Daegu , Republic of Korea., Soladoye AO; a Department of Physiology, Cardiovascular Research Laboratory , College of Health Sciences, University of Ilorin , Ilorin , Nigeria.
Jazyk: angličtina
Zdroj: Archives of physiology and biochemistry [Arch Physiol Biochem] 2017 Dec; Vol. 123 (5), pp. 286-292. Date of Electronic Publication: 2017 May 08.
DOI: 10.1080/13813455.2017.1320681
Abstrakt: Context: Elevated gestational circulating testosterone has been associated with pathological pregnancies that increase the risk of development of cardiometabolic disorder in later life.
Objective: We hypothesised that gestational testosterone exposure, in late pregnancy, causes glucose deregulation and atherogenic dyslipidaemia that would be accompanied by high plasminogen activator inhibitor-1 (PAI-1). The study also hypothesise that low-dose spironolactone treatment would ameliorate these effects.
Methods: Pregnant Wistar rats received vehicle, testosterone (0.5 mg/kg; sc), spironolactone (0.5 mg/kg, po) or testosterone and spironolactone daily between gestational days 15 and 19.
Results: Gestational testosterone exposure led to increased HOMA-IR, circulating insulin, testosterone, 1-h post-load glucose, atherogenic dyslipidaemia, PLR, PAI-1 and MDA. However, all these effects, except that of circulating testosterone, were ameliorated by spironolactone.
Conclusions: These results demonstrate that low-dose spironolactone ameliorates glucose deregulation and atherogenic dyslipidaemia during elevated gestational testosterone exposure, at least in part, by suppressing elevated PAI-1.
Databáze: MEDLINE
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