PREDOCTORAL FELLOWSHIPS FOR STUDENTS WITH DISABILITIES

虽然肥胖与胰岛素抵抗和糖尿病有关这一点已经得到了充分的证实，但潜在的

Although it is well established that obesity is associated with insulin resistance and diabetes, the underlying mechanisms are unknown. Recent findings in our laboratory indicate that c-Jun amino terminal kinase (JNK) signaling pathway may play a role. This proposal addresses the tissue specific effects of JNK1 on the development of insulin resistance during diet-induced obesity. Our hypothesis is that obesity induces macrophage specific JNK, which leads to peripheral insulin resistance. To test this hypothesis, we will: (1) examine mice that receive a bone marrow transplantation from a) JNK deficient mice into wild type mice and b) wild type mice into JNK deficient mice and will be placed on a high fat diet and monitored metabolically, (2) screen for phosphorylation status of JNK substrates in macrophages by employing a JNK kinase that uses an ATP analogue, and (3) analyze the transcriptional profile of insulin resistant macrophages. A better understanding of the molecular mechanism of JNK in macrophages may elucidate obesity's strong association with insulin resistance and diseases of the metabolic syndrome.