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In particular, comparisons between two groups of mice at different time points were performed by ANOVA followed by Bonferroni test, whereas comparisons between two groups of mice at single time points were performed by ANOVA followed by Tukey test. Significance was defined as p?CP-868596 purchase Dystrophy Association MDA202237 (P.P.). ""Obesity has reached epidemic proportions around the world due to a modern PTPRJ lifestyle characterized by increased consumption of foods rich in energy and saturated fat, combined with reduced physical activity (Hill, 2006). This obesity epidemic has resulted in dramatic increases in the incidences of obesity-associated diseases, including type 2 diabetes (T2D), and represents a worldwide health crisis. Numerous studies have shown that insulin resistance precedes the development of hyperglycemia in subjects that eventually develop T2D (Prentki and Nolan, 2006). However, T2D only develops in insulin-resistant subjects after the onset of pancreatic �� cell dysfunction (Leahy, 2005). Inflammation is increasingly known to play a key role in the initiation and development of obesity-associated diseases. For instance, elevated levels of circulating proinflammatory cytokines are observed in obese subjects and those with T2D (Schenk et?al., 2008). Mechanistically, proinflammatory signaling pathways can inhibit insulin signaling, providing a link between inflammation and insulin resistance. By contrast, the involvement of inflammation in �� cell learn more failure in T2D is poorly understood, although a T?cell-mediated autoimmune response against �� cells appears to be a primary pathogenic mechanism in type 1 diabetes (T1D) (Mallone and van Endert, 2008). Recent reports suggest similar inflammatory processes are also activated within T2D islets. For instance, expression of interleukin (IL)-1��, which is involved in the autoimmune processes leading to T1D, is upregulated in the islets of patients and animal models with T2D, and an IL-1 receptor antagonist reportedly improves blood glucose levels and �� cell function in T2D patients (Donath and Shoelson, 2011?and?Larsen et?al., 2007). Accumulation of macrophages within islets has also been observed in T2D subjects (Richardson et?al., 2009), further suggesting activation of inflammation.