Citocinas, disfunção endotelial e resistência à insulina

Abstract

Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.

Relationship between adiponectin, obesity and insulin resistance

“…However, oth-er authors have different ideas and suggest that the inhibition of glucose transport or phosphorylation activity precedes the reduction in glycogen synthesis and glucose oxidation induced by free fatty acids. 21 It should be noted that by increasing intracellular metabolites of fatty acids, there may be activation of the serine/threonine kinase cascade, possibly via protein kinase C delta, leading to the phosphorylation of serine/ threonine in the substrate for the insulin receptor 1 (IRS-1). Phosphorylated IRS-1 of serine does not bind or activate phosphatidylinositol 3-kinase (PI-3K), resulting in decreased transport of glucose and other manifestations of insulin resistance.…”

Association between sex hormone-binding globulin (SHBG) and metabolic syndrome among men

“…19 CRP is the best studied and best characterized inflammatory marker. Kupelian et al, 20 in a recent non-interventional population-based study examining 2,301 men aged 30-79 years, and Gannagé-Yared, 13 in a cross-sectional study on young men, reported an inverse association between the levels of SHBG and CRP, thus corroborating the inverse association between SHBG and insulin resistance.…”

Efeitos de diferentes graus de sensibilidade a insulina na função endotelial de pacientes obesos

“…Triglyceride level is directly related to the presence of central obesity, causing increased lipolysis and leading both to insulin resistance and endothelial dysfunction through increased expression of markers of inflammation such as C-reactive protein, IL-6, soluble adhesion molecules, von Willebrand factor and endothelin-1 31 . In addition, clinical and experimental studies have shown that free fatty acids change vasodilatory response of endothelium by inhibiting eNOS and stimulating anion expression by endothelial and vascular cells via NADPH oxidase, thereby lowering NO bioavailability 32 . In spite of the controversy on their role as an independent cardiovascular risk factor 33 , triglycerides are directly related to other non-lipid cardiovascular factors such as microalbuminuria and insulin resistance 34 .…”