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

Inactive Publication Date: 2012-07-04
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Studies have reported that using GGPPS as a drug target can improve osteoblast differentiation and bone construction (Weivoda and Hohl 2011), and some studies have also demonstrated that GGPPS ca

Method used

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  • Application of geranylgeranyl diphosphate synthase (GGPPS) antagonist in preparation of medicament for treating II-type diabetes mellitus
  • Application of geranylgeranyl diphosphate synthase (GGPPS) antagonist in preparation of medicament for treating II-type diabetes mellitus
  • Application of geranylgeranyl diphosphate synthase (GGPPS) antagonist in preparation of medicament for treating II-type diabetes mellitus

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Experimental program
Comparison scheme
Effect test

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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PUM

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Abstract

The invention discloses application of geranylgeranyl diphosphate synthase (GGPPS) for treating II-type diabetes mellitus, and particularly provides application of a GGPPS antagonist in preparation of medicament for treating the II-type diabetes mellitus. The GGPPS gene and protein antagonist capable of being used for preparing sensitization medicaments is firstly disclosed. Furthermore, the GGPPS antagonist facilitates improvement on sensibility of insulin target organization on insulin, enhances treatment effects of the insulin, improves life quality of II-type diabetics, and has potential and good application prospect in the field of the II-type diabetes mellitus treatment.

Description

technical field [0001] The present invention relates to the application of GGPPS in the drug treatment of type II diabetes, in particular to the application of GGPPS antagonist in the preparation of the drug for treating type II diabetes. Background technique [0002] Type 2 diabetes, also known as non-insulin-dependent diabetes or adult-onset diabetes, is a metabolic disease with multiple etiologies. There are many factors for its pathogenesis. In addition to internal genetic factors, it also has a great relationship with people's living environment, lifestyle and behavior. In particular, some metabolic disorders caused by excessive obesity can easily lead to type Ⅱ diabetes. In addition, 90% of patients develop the disease after the age of 35-40. [0003] Type 2 diabetes is mainly manifested by the patient's muscle and adipose tissue can develop resistance to insulin, and as compensation, the pancreatic beta cells secrete more insulin, but still cannot maintain blood suga...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61P3/10
Inventor 薛斌李朝军沈宁郁晓陆克
Owner NANJING UNIV
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