Interaction between angiotensin endothelium and insulin resistance

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Insulin resistance is associated with metabolic syndrome, which increases the risk of adverse cardiovascular outcomes. There is definitive evidence that insulin resistance and endothelial dysfunction progress in parallel. As insulin resistance progresses to clinical metabolic syndrome, impaired glucose tolerance, and development of diabetes, there is a parallel track that leads from endothelial dysfunction to inflammation, with increased oxi-dative stress leading to overt atherosclerotic disease. Insulin resistance has been shown to interact with this parallel track of endothelial dysfunction through the accumulation of free fatty acids, proinflammatory adipokines, and TNF alpha [59]. In addition, increased oxidative stress, oxidation of LDL, the reduction of HDL, and the development of hypertension, hyperuricemia, and hy-perglycemia contribute to the mechanisms of underlying endothelial dysfunction in insulin resistance [51].

Because angiotensin II plays a significant role in endothelial dysfunction, the interplay of angio-tensin II in glucose homeostasis has been of significant interest to biochemical and molecular biologists. The relationships between angiotensin II and insulin signaling pathways are becoming evident in preclinical studies. Insulin binds to the cell surface receptor tyrosine kinase, which leads to autophosphorylation of the tyrosine residue that turns on the insulin signaling pathways. The initial step is activation of phosphatidyl inositol kinase (PI-3K) pathway, which is important for glucose transport in skeletal muscle. In addition, this pathway enhances nitric oxide production and insulin-induced vasodilatory response [60,61]. The second pathway that is activated is the mitogen activated protein kinase (MAPK). This pathway promotes vascular smooth muscle cell proliferation and migration induced by insulin, thrombin, and platelet derived growth factors (Fig. 4). In addition, a third pathway is triggered that leads to activation of P70 S6 kinase, a regulator of protein synthesis [62-64].

Angiotensin II plays an important role in signaling pathways for maintaining structure and function of the heart. Angiotensin I stimulation results in activation of the MAPK, PI-3K, and tyrosine phosphorylation both in vivo and vitro. In the heart, angiotensin II blocks insulin-induced PI-3K but stimulates MAPK, thus inhibiting the metabolic but not the proliferative effects of insulin [65]. This crosstalk between the two signaling pathways may play a pivotal role in explaining how cardiovascular and neuroendocrine physiology relate to each other and thus explain the role of angiotensin II blockade in insulin resistance and prevention of diabetes.

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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