T2D accounts for approximately 90–95% of patients with diabetes, with individuals having disease pathogenesis ranging from predominantly insulin resistance with relative insulin deficiency to primarily an insulin secretory defect with accompanying Selleck PI3K inhibitor insulin resistance. Historically, T2D has been considered

to be a metabolic disease of the ageing individual and has not been considered to be autoimmune. Recently, many notable discoveries have provided evidence to support the concept of immune system involvement in obesity and type 2 diabetes development [16–19]. Chronic inflammation of the visceral adipose tissue is believed to be involved in the pathogenesis of insulin resistance and subsequent development of T2D, with multiple groups demonstrating an increase selleck chemical in visceral adipose T cell subsets [20–23]. In fact, proinflammatory T cells present in visceral fat are believed to be involved in the initial establishment of adipose inflammation preceding the infiltration of monocytes into the adipose

tissue [20]. Regulatory T cells have been shown to be highly enriched in the abdominal fat of normal mice but reduced significantly in the abdominal fat of insulin-resistant mouse models of obesity [24]. Deiuliis et al. [25] reported that obesity in mice and humans actually results in adipose T regulatory cell depletion. In fact, induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice [26]. Moreover, Meijer K et al. [27] reported that human adipocytes express a number of cytokines and chemokines that are able to induce inflammation and activate CD4+ cells independent

of macrophages. These results suggest that the primary event in the sequence leading to chronic inflammation in adipose tissue is a metabolic change in adipocytes inducing production of immunological mediators, and presentation of potential P-type ATPase antigens by adipocytes leading to activation of adipose tissue macrophages and other immune cells. Furthermore, many studies, both cross-sectional and prospective, have demonstrated elevated levels of circulating acute phase proteins as well as cytokines and chemokines in patients with T2D, supporting the concept that T2D is an inflammatory disease [28–31]. The diagnosis of T2D involves insulin resistance as one of the components in the diabetes disease process. In recent years, the contribution of several proinflammatory cytokines such as interleukin (IL)-1β[32–34], IL-6 [35] and tumour necrosis factor (TNF)-α[36,37] have been implicated in disrupting insulin signalling, causing insulin resistance. In fact, neutralizing TNF-α in rats provided an early suggestion that inflammatory mediators were associated with the development of insulin resistance [36]. Irrespective of the initiation trigger for the chronic inflammation, the involvement of chronic inflammation in the development of insulin resistance and subsequent development of T2D is now widely accepted.