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Insulin signaling cascade is vital for normal glucose homeostasis. In our previous study, we have demonstrated that chronic inflammation of the liver is associated with the progression of insulin resistance. However, it is not clear whether inflammation mediates hepatic insulin resistance directly or indirectly through other factors. Here we showed that hepatic insulin resistance occurred in NOD mice, an animal model of autoimmune diabetes, with increased level of IL-4 in plasma. To investigate the cellular and molecular mechanism involved in this phenomenon, primary hepatocytes were isolated from NOD mice and NOD/SCID chimeras. The results showed that the sera from NOD mice could induce hepatic insulin resistance, including inhibition of insulin signal transduction and the phosphorylation of Akt and AS160, a negative regulator of insulin signaling cascade. In NOD mice, the peripheral IL-4 level is markedly elevated, which are negatively correlated with insulin sensitivity of hepatocytes. Hepatic expression of IL-4R, a receptor for IL-4, is increased in NOD mice. Furthermore, IL-4 could bind to hepatocyte surface receptors and induce receptor-mediated insulin signaling inhibition in hepatocytes. These findings suggest that the high levels of IL-4 in serum of NOD mice may directly inhibit hepatocyte insulin signaling, leading to hepatic insulin resistance. It should be emphasized that this impaired insulin signaling is not dependent on inflammatory cytokines, since it remains in NOD/SCID chimeras. Taken together, our findings demonstrate that inflammation directly mediates hepatic insulin resistance.2
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He could have loaded and started the game. He didn’t have the time for a continued warm up session. If this was the last match played before the break, there would have been no point in continuing. Once the loss to Cleveland was confirmed, this was a perfectly reasonable reason to stop the warm up session. I’d be surprised if this wasn’t the case. If you watch the game, the Cavs lead seemed to have occurred after a few minutes of warm up.

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