Application of geranylgeranyl diphosphate synthase (GGPPS) antagonist in preparation of medicament for treating II-type diabetes mellitus
An antagonist and diabetes technology, applied in gene therapy, drug combination, metabolic diseases, etc., to achieve good application prospects, enhance curative effect, and improve the quality of life
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Embodiment 1
[0086] Establishment of insulin resistance cell model
[0087] According to the method in the previous section "General Materials and Methods", we induced and established insulin resistant cell models. After adipocytes were induced with TNF-α cytokine for 3 days, the changes of tyrosine phosphorylation level of IRS in the insulin signaling pathway were detected by immunoblotting. like figure 1 As shown in A. After TNF-α cytokine induction, the tyrosine phosphorylation level of IRS was significantly decreased.
[0088] We examined the extent of glucose uptake in insulin resistant cells. like figure 1 As shown in B, the degree of glucose uptake by insulin-resistant cells is significantly reduced after insulin stimulation.
[0089] The above results indicated that the insulin resistance cell model was successfully established.
Embodiment 2
[0091] Changes of GGPPS in insulin resistance model
[0092] We detected the level change of GGPPS in the insulin resistant cell model after insulin stimulation by immunoprecipitation. like figure 2 As shown, GGPPS was significantly increased in the insulin resistant cell model by insulin stimulation.
Embodiment 3
[0094] Interfering with GGPPS restores sensitivity to insulin in insulin-resistant cells
[0095] We used the Ade-ggpps / siRNA recombinant adenovirus constructed in the previous section "General Materials and Methods" to interfere with the expression of GGPPS in insulin-resistant cells. At different time points after insulin stimulation, we examined the level of p-Erk1 / 2. like image 3 As shown, p-Erk1 / 2 levels were significantly reduced in insulin-resistant cells in which GGPPS expression was disturbed compared to controls. This suggests that interfering with GGPPS restored the sensitivity of insulin-resistant cells to insulin.
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