Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor- , and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarification of the regulatory processes about hepatic insulin resistance by adipokines in rodents and human would seem essential in order to understand the mechanism of type 2 diabetes and for developing novel therapeutic strategies to treat it. 1. Introduction In many developed and developing countries, obesity has reached epidemic proportions, resulting in an increasing prevalence of type 2 diabetes characterized by insulin resistance of peripheral tissues such as liver, muscle, and fat which cannot be overcome by hypersecretion of pancreatic beta cells [1]. One survey conducted in 2000 revealed that more than 150 million people in the world suffered from type 2 diabetes [2] and 80% of these cases were related to obesity. Because various studies have demonstrated that hepatic insulin resistance plays a central role in the development of type 2 diabetes and obesity is centrally involved in increasing the clinical risk of diabetes, visceral adipose tissue is now thought to provide a link between obesity and hepatic insulin resistance. Adipose tissue was traditionally regarded as a passive energy reservoir. However, since the discovery of leptin and subsequent identification of other adipose tissue-derived cytokines (e.g., adiponectin and resistin) in the last two decades [3], it became clear that adipose tissue is an active endocrine organ. Obese adipose tissue also secretes various inflammatory cytokines, such as interleukin-6 (IL-6) and tumour necrosis factor- (TNF- ) [4]. All of these cytokines, termed adipokines, act in an autocrine, paracrine, or endocrine fashion to control various metabolic functions. Some of these adipokines have been implicated in the development of hepatic insulin resistance. Indeed, they may act locally or distally to alter insulin sensitivity in insulin-targeted organs such as liver which is also discussed in detail by Marra and Bertolani [5] previously or may act through neuroendocrine, autonomic, or immune pathways. For example, activation of proinflammatory pathways in adipose tissue is known to interfere with insulin signaling and induce
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