| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
We found that U73122,which was phospholioase C(PLC) inhibitor, blocked insulin-induced glucose uptake in 3T3-L1 adipocytes. Moreover, overexpression of PLCγ stimulated glucose uptake without insulin stimulation in a dose dependent manner. Overexpression of PLCγ did not affect phosphorylation of Akt, but enhanced phosphorylation of atypical PKC. Thus, it suggests that PLCγ stimulates gluxoce uptake through activation of atypical PKC.
Overexpression of protein phosphatase 2C(PP2C) caused dephosphorylation of serine residue of p85 of PI 3-kinase, and positively regulated insulin signaling. On the other hand, overexpression of PP2C accelerated insulin-stimulated IRS-1 degradation. When we suppressed PP2C protein expression by sRNA interference method, insulin-induced IRS-1 degradation was inhibited. Moreover, PP2C-induced IRS-1 degradation was completely inhibited by lactasistine treatment, which was proteasome inhibitor. PI 3-kinase inhibitor, wortmannin, also suppressed it, partially. Taken together, PP2C has both positive and negative effects on insulin signaling through PI 3-kinase pathway.
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