Hadjadj Leila, Várbíró Szabolcs, Horváth Eszter Mária, Monori-Kiss Anna, Pál Éva, Karvaly Gellért Balázs, Heinzlmann Andrea, Magyar Attila, Szabó István, Sziva Réka Eszter, Benyó Zoltán, Buday Mariann, Nádasy György László
1 Institute of Human Physiology and Clinical Experimental Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
2 2nd Department of Obstetrics and Gynecology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Diab Vasc Dis Res. 2018 Jul;15(4):294-301. doi: 10.1177/1479164118758580. Epub 2018 Feb 21.
Hyperandrogenic state in females is accompanied with metabolic syndrome, insulin resistance and vascular pathologies. A total of 67%-85% of hyperandrogenic women suffer also from vitamin D deficiency. We aimed to check a potential interplay between hyperandrogenism and vitamin D deficiency in producing insulin resistance and effects on coronary resistance arteries. Adolescent female rats were divided into four groups, 11-12 animals in each. Transdermal testosterone-treated and vehicle-treated animals were kept either on vitamin D-deficient or on vitamin D-supplemented diet for 8 weeks. Plasma sexual steroid, insulin, leptin and vitamin D plasma levels were measured, and oral glucose tolerance test was performed. In coronary arterioles, insulin receptor and vitamin D receptor expressions were tested by immunohistochemistry, and insulin-induced relaxation was measured in vitro on isolated coronary resistance artery segments. Testosterone impaired glucose tolerance, and it diminished insulin relaxation but did not affect the expression of insulin and vitamin D receptors in vascular tissue. Vitamin D deficiency elevated postprandial insulin levels and homeostatic model assessment insulin resistance. It also diminished insulin-induced coronary arteriole relaxation, while it raised the expression of vitamin D and insulin receptors in the endothelial and medial layers. Our conclusion is that both hyperandrogenism and vitamin D deficiency reduce sensitivity of coronary vascular tissue to insulin, but they do it with different mechanisms.
女性高雄激素状态伴有代谢综合征、胰岛素抵抗和血管病变。67% - 85%的高雄激素女性还存在维生素D缺乏。我们旨在研究高雄激素血症与维生素D缺乏在产生胰岛素抵抗以及对冠状动脉阻力动脉的影响方面的潜在相互作用。将青春期雌性大鼠分为四组，每组11 - 12只。经皮给予睾酮处理的动物和给予赋形剂处理的动物分别给予维生素D缺乏或补充维生素D的饮食8周。检测血浆性类固醇激素、胰岛素、瘦素和维生素D水平，并进行口服葡萄糖耐量试验。在冠状动脉小动脉中，通过免疫组织化学检测胰岛素受体和维生素D受体的表达，并在体外对分离的冠状动脉阻力动脉段测量胰岛素诱导的舒张。睾酮损害葡萄糖耐量，降低胰岛素诱导的舒张，但不影响血管组织中胰岛素和维生素D受体的表达。维生素D缺乏会升高餐后胰岛素水平和稳态模型评估胰岛素抵抗。它还会降低胰岛素诱导的冠状动脉小动脉舒张，同时增加内皮和中层维生素D和胰岛素受体的表达。我们的结论是，高雄激素血症和维生素D缺乏都会降低冠状动脉血管组织对胰岛素的敏感性，但它们的机制不同。
