鞘氨醇激酶2（SphK2）定位于细胞核及内质网，能够通过合成细胞内S1P参与肥胖及胰岛素抵抗的调节，近年发现，其能够与HDAC1/2形成抑制复合体调节基因表达。我们发现抑制SphK2能够抑制肝糖异生相关基因PEPCK和G6Pase表达并改善糖尿病小鼠胰岛素抵抗，但具体机制有待研究，我们前期结果还显示HDAC1/2和p-STAT3可能参与调节糖异生相关基因表达。为此，我们提出科学假设：SphK2通过与HDAC1/2形成抑制复合体或者调节STAT3磷酸化及入核影响PEPCK和G6Pase表达。基于假说，本研究将通过细胞和动物实验首先明确SphK2与HDAC1和2形成的抑制复合体是否调节PEPCK和G6Pase表达；若非通过HDAC1/2调节，则进一步明确SphK2是否通过p-STAT3入核调节PEPCK和G6Pase表达。对SphK2调节肝糖异生机制的揭示，将为胰岛素抵抗的研究提供新的思路。

Sphingosine kinase 2 (SphK2) is found mainly in nucleus and endoplasmic reticulum，and regulates obesity and insulin resistance through synthesis of intracellular S1P, it has been found that SphK2 reglates gene expression in form supressor complex with HDAC1/2. in our previous research, inhibition of SphK2 was found ameliorating expression of gluconeogenetic gene and peripheral insulin resistance of diabetic mice, but the mechenism remains to be uncovered. We found also HDAC1/2 and p-STAT3 participated also in the regulation of neogenetic genes. In this proposal, we hypothesize that SphK2 regulated hepatic gluconeogenetic gene PEPCK and G6Pase expression through fomation of supressor complex with HDAC1/2 or nuclear import of STAT3. Based on this hypothesis, we will make asure whether supressor complex of SphK2 and HDAC1/2 participate in the regulation of the expression of PEPCK and G6Pase; If not, we will futher find out whether nuclear import of STAT3 play a role on the regulation of PEPCK and G6Pase expression; Answer for the regulatory mechanism of SphK2 on gluconeogensis will provide ideas for exploring insulin resistance.