The Pathophysiological Role of Protein Phosphatase 2A (PP2A) in metabolic Syndrome

我们发现棕榈酸酯和c2 -神经酰胺的预孵育通过抑制3T3-L1脂肪细胞中的Akt诱导胰岛素抵抗。棕榈酸酯的抑制作用被。肉豆蔻素，神经酰胺合成抑制剂。肉豆蔻酸盐或油酸盐，这不是神经酰胺的前体，没有引起胰岛素抵抗。我们还发现，棕榈酸和冈田酸可刺激PP2A活性，而PP2A抑制剂可阻断棕榈酸诱导的Akt抑制。这些结果表明棕榈酸酯通过在脂肪细胞中重新合成神经酰胺激活Akt来抑制Akt。另一方面，虽然棕榈酸酯和c2 -神经酰胺对Fao大鼠肝癌细胞中Akt的抑制作用与对3T3-L1脂肪细胞的抑制作用相同，但这种抑制作用并不伴随着PP2A的激活。支持这一结果的是，冈田酸或肉豆蔻素不能阻断棕榈酸诱导的Akt抑制。这些结果表明，PP2A激活或神经酰胺合成与棕榈酸盐诱导的Fao细胞胰岛素抵抗无关。最后，在L6肌细胞中，棕榈酸酯和c2 -神经酰胺诱导的Akt抑制被部分阻断。肉豆蔻酸不抑制Akt，肉豆蔻酸部分阻断棕榈酸的作用。综上所述，棕榈酸盐在不同的细胞类型中通过不同的机制引起胰岛素抵抗

We have found that preincubation of palmitate and C2-ceramide induced insulin resistance through inhibiting Akt in 3T3-L1 adipocytes. The inhibitory effect of palmitate was blocked by. myriocin, ceramide synthesis inhibitor. Myristate or oleate, which are not the precursor of ceramide, did not cause insulin resistance. We also found that PP2A activity was stimulated by palmitate and okadaic acid, PP2A inhibitor, blocked palmitate-induced Akt inhibition. These results suggest that palmitate inhibits Akt through activating Akt by de novo synthesis of ceramide in the cells in adipocytes.On the other hand, although, palmitate and C2-ceramide inhibited Akt in Fao rat hepatoma cells as same as in 3T3-L1 adipocytes, the inhibition was not accompanied by PP2A activation. In support of this result, okadaic acid or myriocin did not block palmitate-induced Akt inhibition. These results suggest that either PP2A activation or ceramide synthesis is not involved in palmitate-induced insulin resistance in Fao cells.Finally, in L6 myocytes, palmitate and C2-ceramide induced Akt inhibition was partially blocked okadaic acid. Myristate did not inhibit Akt and myriocin partially blocked palmitate' s effect. In conclusion, palmitate causes insulin resistance through different mechanisms among different cell types