Further analysis of its relationship with ARRY-142886 606143-52-6 insulin sensitivity will provide additional evidence for its actions on insulin resistance in humans. In addition, given the chemotactic activities of MK towards macrophages, which play a central role in obesity-induced inflammation and insulin resistance, future studies will also investigate the involvement of MK in macrophage recruitment into adipose tissue during obesity. Though MK attenuates insulin signaling in adipocytes, the signal events by which MK interacts with insulin signal transduction remain to be clarified. The STAT3-SOCS3 pathway has been demonstrated to play a critical role in insulin resistance. On activation, STAT3 dimerizes and translocates to the nucleus, inducing the expression of SOCS3, which in turn inhibits insulin signaling by direct interaction with the insulin receptor and by preventing the coupling of IRS-1 with the insulin receptor. To date, a range of adipokines have been reported to promote insulin resistance in adipocytes through the STAT3-SOCS3 pathway. In this study, we observed that MK also activated the STAT3-SOCS3 pathway in 3T3-L1 adipocytes, consistent with previous studies showing stimulative effects of MK on STAT3 in preadipocytes and keratinocytes. Thus, MK is a potent activator of the STAT3-SOCS3 signaling cascade, which may mediate the inhibitory effects of MK on insulin signaling in adipocytes. Another question not addressed is how MK activates the STAT3-SOCS3 pathway in adipocytes. Previous studies have proposed multiple molecules as the receptor of MK, including anaplastic lymphoma kinase, protein-tyrosine phosphatase f, low density lipoprotein receptor-related protein and integrin. Among them, ALK is a transmembrane receptor tyrosine kinase that has been shown to activate STAT3. Additionally, we detected ALK expression in adipocytes. Thus, it may be through ALK that MK activates the STAT3-SOCS3 pathway in adipocytes, which further impairs insulin signal transduction, as illustrated in Figure 9. In summary, we show here that MK is expressed in adipocytes and is associated with obesity in both mice and humans. Moreover, as revealed by reduced phosphorylation of Akt and IRS-1 and decreased GLUT4 translocation in response to insulin stimulation, MK suppresses insulin signaling in adipocytes, associated with activation of the STAT3-SOCS3 signaling pathway. Therefore, MK is a potential link between obesity and insulin resistance, and may offer a new target to treat insulin resistance and other obesity-associated diseases. The DNA-binding protein high mobility group AT-hook 2 and the zinc finger protein PLAG1 share a common role in the molecular pathogenesis of certain benign tumors, e. g. of the salivary glands and of adipose tissue. Pleomorphic adenomas are benign tumors of myoepithelial origin most often located in the parotid glands. Based on the existence of clonal chromosomal aberrations cytogenetic subtypes of pleomorphic adenomas can be distinguished. Of these, structural rearrangements involving chromosomal regions 8q12 and 12q14,15 are most frequently observed.