Insulin resistance in an animal model of polycystic ovary disease is aggravated by vitamin D deficiency: Vascular consequences

Abstract

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.

Vitamin D Deficiency Induces Elevated Oxidative and Biomechanical Damage in Coronary Arterioles in Male Rats

“…On the other hand, in case of vitamin-D-dependency, the organ or tissue cannot adapt by receptor-upregulation to the concentration changes, so it will be sensitive and vulnerable to vitamin D deficiency. According to our previous results from animal experiments, small vessels from the heart and brain are vitamin-D-dependent tissues, because in extreme vitamin-D-deficient milieu, they go through major changes [ 18 , 19 , 23 , 37 , 42 ], but these alterations are depending on which region the vessels are originated from. Both vitamin D deficiency and toxicity can induce smaller carotid artery diameter and larger wall thickness in male Wistar rat models within 4 weeks [ 43 ].…”

“…They were supplied with tap water and food ad libitum for the following 8 weeks. Vitamin D supplemented animals ( n = 11, served as “Control” group) were fed with conventional rat chow (SM Rat/mouse normal diet S8106-S011, Ssniff Spezialdiäten GmbH, Soest, Germany), which was supplemented with per os vitamin D (Vigantol, 20.000 IU/mL, Merck/Serono, Mumbai, India) to reach 300 IU/kgbw daily dose that can be considered for optimal vitamin D supply [ 18 ].…”

Vitamin D and macrophage polarization in epicardial adipose tissue of atherosclerotic swine

“…The presence of VDR in most of the tissues provides a mechanistic link between vitamin D deficiency and the pathophysiology of the disorders. Recently, increased VDR expression in the medial smooth muscle cells of the coronary artery was observed in vitamin D deficient rats [ 22 ]. Although the exact mechanism is still unclear, the report suggests that the insulin- mediated coronary arteriole relaxation was affected in the absence of vitamin D and this correlates with increased expression of VDR.…”

Nontargeted metabolomic analysis of skeletal muscle in a dehydroepiandrosterone‐induced mouse model of polycystic ovary syndrome

“…About 67 to 85% of hyperandrogenic women also suffer from vitamin D deficiency. In a testosterone‐induced PCOS rat model, vitamin D deficiency aggravated IR (Hadjadj et al, ). Moreover, several longitudinal observational studies have shown that vitamin D‐deficient subjects have a higher risk of developing type 2 diabetes (Knekt et al, ; Pittas, Sun, Manson, Dawson‐Hughes, & Hu, ).…”