Dihydrotestosterone deteriorates cardiac insulin signaling and glucose transport in the rat model of polycystic ovary syndrome.
It is supposed that women with polycystic ovary syndrome (PCOS) are prone to develop cardiovascular disease as a consequence of multiple risk factors that are mostly related to the state of insulin resistance and consequent hyperinsulinemia. In the present study, we evaluated insulin signaling and glucose transporters (GLUT) in cardiac cells of dihydrotestosterone (DHT) treated female rats as an animal model of PCOS. Expression of proteins involved in cardiac insulin signaling pathways and glucose transporters, as well as their phosphorylation or intracellular localization were studied by Western blot analysis in DHT-treated and control rats. Treatment with DHT resulted in increased body mass, absolute mass of the heart, elevated plasma insulin concentration, dyslipidemia and insulin resistance. At the molecular level, DHT treatment did not change protein expression of cardiac insulin receptor and insulin receptor substrate 1, while phosphorylation of the substrate at serine 307 was increased. Unexpectedly, although expression of downstream Akt kinase and its phosphorylation at threonine 308 were not altered, phosphorylation of Akt at serine 473 was increased in the heart of DHT-treated rats. In contrast, expression and phosphorylation of extracellular signal regulated kinases 1/2 were decreased. Plasma membrane contents of GLUT1 and GLUT4 were decreased, as well as the expression of GLUT4 in cardiac cells at the end of androgen treatment. The obtained results provide evidence for alterations in expression and especially in functional characteristics of insulin signaling molecules and glucose transporters in the heart of DHT-treated rats with PCOS, indicating impaired cardiac insulin action.
Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. Electronic address: sradivojsa@vinca.rs.
Snežana
S
Tepavčević
Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia. Electronic address: dvojnovic@ibiss.bg.ac.rs.
Danijela
D
Vojnović Milutinović
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: djmacut@gmail.com.
Djuro
D
Macut
Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. Electronic address: zzakula@vinca.rs.
Zorica
Z
Žakula
Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia. Electronic address: mnikolic@ibiss.bg.ac.rs.
Marina
M
Nikolić
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: dr.ivana.bozic@gmail.com.
Ivana
I
Božić-Antić
Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. Electronic address: snjezana.romic@vinca.rs.
Snježana
S
Romić
CHC Bežanijska kosa, Belgrade, Serbia. Electronic address: jbjekic@yahoo.com.
Jelica
J
Bjekić-Macut
Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia. Electronic address: gormatic@ibiss.bg.ac.rs.
Gordana
G
Matić
Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. Electronic address: gogi@vinca.rs.
Goran
G
Korićanac
D000818:Animals; D001692:Biological Transport; D013196:Dihydrotestosterone; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D013196:Dihydrotestosterone; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose
Dihydrotestosterone; Glucose transporters; Heart; Insulin signaling pathway; Polycystic ovary syndrome