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The role of adipose tissue in insulin resistance and inflammation - the way to obesity and type 2 diabetes


Adipose tissue (AT), in contrast to skeletal muscle, accounts for a small part of the insulin-stimulated glucose disposal. Skeletal muscle has been the focus of most research to define mechanisms for peripheral insulin resistance (IR), adipose tissue has long been neglected. However, studies have shown that AT not only stores and releases energy as lipids, it is also the largest endocrine organ. Several factors secreted by AT, such as free fatty acids and adipokines, have been shown to affect insulin sensitivity not only in AT but also in other tissues. These factors are altered in IR states and they are likely to play an important role in the development of congestive heart failure (CHF). Excess of AT increases the risk of a number of conditions including coronary artery disease and diabetes. We will study the molecular mechanisms of IR and inflammation, focusing on the function of the adipocyte in CHF. Recent work tried to correlate changes in several cytokines with the progression and poor prognosis of CH F. However, little is known about the impact of adipose tissue in this condition, we aim at clarifying the relationships between CHF, IR, diabetes, its drug therapy and cytokine levels. We will try to understand if signalling pathways utilized by insulin and inflammatory mediators, in normal and IR states, are different or if they are the same. In addition, we want to elucidate the effects of immunosuppressive agents (IA) administration on IR and the action of insulin in cultured cells and rodents and study the role of adipocytes in this condition. IA may play a role in the development of IR, but the precise mechanisms are not well understood. It maybe that IA administration causes imbalances in systemic glucose and lipid metabolism at the level of the adipocyte. IR maybe an impaired ability to store fat in AT which in turn leads to lipid accumulation in liver and skeletal muscle and this dysregulation maybe associated with abnormal expression of cytokines.

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