| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
1)Roles of mTOR and INK in insulin or anisomycin-induced IRS-1 serine phosphorylation.
In 3T3-L1 adipocytes, insulin-induced phosphorylation of IRS-1 on Ser 307, ser 612, and Ser 636/639 was reduced by rapamycin, and was further inhibited by the combination with JNK inhibitor, SP 600125. Anisomycin-induced phosphorylation on the same residues was inhibited both rapamycin and SP 600125. Unlike insulin, anisomycin failed to elicit translocation or degradation of IRS-1. Therefore, mTOR and JNK pathways play the same IRS-1 serine phosphorylation, but are different in IRS-1 translocation and degradation.
2)IL-1α and IRS-1 serine phosphorylation.
IRS-1 was transiently phosphorylated on some serine residues around 15min after IL-1 stimulation, when several serine kinases, IKK, JNK, ERK, and p70S6K were activated. Tyrosine phosphorylation of IRS-1 was recovered only by IKK inhibitor or JNK inhibotor, suggesting the specific involvement of these two kinases. Insulin-stimulated Akt phosphorylation and 2-deoxyglucose uptake were not inhibited by IL-1. Akt phosphorylation was synergistically inhibited by IL-1 in the presence IL-6. Thus, short term IL-1 treatment transiently causes insulin resistance at the level of IRS-1 with its serine phosphorylation. IL1 may suppress insulin signaling downstream of IRS-1 in the presence of other cytokines, such as IL-6.
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