Metabolites of lipid metabo lism such as diacylglycerol have been technical support shown to directly induce insulin resistance by chronically activating protein kinase C. PKC activation terminates insulin signal ing, preventing crucial tyrosine phosphorylation by the insulin receptor, leading to impaired insulin signaling. MetS is also associated with a state of chronic inflam mation. Adipocyte leakage has recently been shown to result in the recruitment of macrophages, which envelope excess lipids, form foam cells, and release inflammatory cytokines, setting up a state of systemic, chronic inflam mation. These adipokines Inhibitors,Modulators,Libraries lead to the systemic activation of several protein kinases involved in inflam matory signal transduction, including phosphoinositide 3 kinase, glycogen synthase kinase and PKC that singly or in concert cause insulin resistance in skeletal muscle and adipose tissue.

Hence, thera pies which reduce circulating lipids and reduce systemic inflammation have shown promise in the treatment of insulin resistance and MetS. Lifestyle modifications including diet and exercise are rec ommended as first line intervention for Inhibitors,Modulators,Libraries treating insulin resistance and MetS by the National Cholesterol Educa tion Program Inhibitors,Modulators,Libraries and American Heart Association. The Mediterranean style diet, high in plant foods and monounsaturated fatty acids and low in processed foods and refined carbohydrates, has been shown to reduce CVD risk factors and inflammatory burden associated with MetS etiology. Pharmacologic treat ment is considered appropriate if the individual is refrac tory to a lifestyle approach.

A recent review of the literature reveals that both intensive lifestyle modifica tions and drugs such as rimonabant or rosiglitazone may reduce the prevalence of MetS in 25 33% of patients. While new pharmacologic approaches to MetS are under development, relying on drug Inhibitors,Modulators,Libraries therapy for an epidemic caused by a maladaptive diet is not as rational as realigning dietary habits. These findings suggest that new lifestyle modification approaches in the treatment of MetS and its complications should be important public health priorities. Advancing knowledge in inflammation and insulin sign aling suggest that reversing the chronic imbalances of Inhibitors,Modulators,Libraries these downstream kinases provides a promising and logi cal strategy for reducing insulin resistance and the meta bolic abnormalities of MetS.

Inhibition of downstream kinases could be accomplished by using pharmaceuticals such as sunitinib and imatinib, approved to treat cancers but which may also cause remission of diabetes. However, selleck chemicals Ivacaftor several dietary phytochemicals, such as genistein and curcumin, have been shown to be protein kinase inhibitors. A recent study showed that combining additional dietary polyphenols with a Mediterranean diet could provide syn ergistic effects and positively impact postprandial dysme tabolism.