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Application of MG53 gene to treatment of insulin resistance, type II diabetes mellitus and related diseases thereof

A technology for insulin resistance and related diseases, used in gene therapy, metabolic diseases, cardiovascular system diseases, etc., can solve problems such as liver damage, aggravate heart burden, increase blood volume, etc., to promote glucose metabolism, inhibit obesity, and reduce adverse effects. effect of reaction

Active Publication Date: 2010-12-15
BOYA PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] 4) Insulin sensitizers work by activating PPAR-, and their biggest side effects are liver damage and increased blood volume, thereby increasing the burden on the heart
The MG53 protein, which is known to be expressed by the MG53 gene, is expressed only in the heart and skeletal muscle, the largest insulin target organs throughout the body (7)( figure 1 ), it is speculated that the expression of MG53 gene may be related to the function of insulin

Method used

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  • Application of MG53 gene to treatment of insulin resistance, type II diabetes mellitus and related diseases thereof
  • Application of MG53 gene to treatment of insulin resistance, type II diabetes mellitus and related diseases thereof
  • Application of MG53 gene to treatment of insulin resistance, type II diabetes mellitus and related diseases thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0058] Example 2 Overexpression of MG53 in adult rat cardiomyocytes inhibits insulin-mediated glucose uptake

[0059] (1) Overexpression of MG53 in adult rat cardiomyocytes

[0060] Take the heart of an 8-week-old male SD rat, separate the cells by enzymatic perfusion, plant the cells in a culture dish (10), and infect with 200 moi of GFP or GFP-MG53 adenovirus (Ad-GFP or Ad-GFP-MG53) for 48 hours , observe the transfection efficiency under a fluorescence microscope, and the cells infected with adenovirus can show fluorescence under a fluorescence microscope ( Figure 4 ). Protein was extracted for SDS-PAGE-immunoblotting test (Western blot) to detect the protein content of MG53 ( Figure 5 A), Determining the efficiency of MG53 overexpression ( Figure 5 B). Figure 4 and Figure 5 It shows that in Ad-GFP-MG53-infected rat cardiomyocytes, MG53 has been overexpressed (*: p<0.001 vs GFP group, the results of at least 6-8 experiments in each group).

[0061] (2) Detection ...

Embodiment 3

[0063] Example 3 Overexpression of MG53 in adult rat cardiomyocytes inhibits insulin receptor signal transduction

[0064] (1) The method for overexpressing MG53 in adult rat cardiomyocytes is the same as that described in (1) in Example 2.

[0065] (2) To detect the inhibition of insulin receptor signal transduction by overexpression of MG53 in adult rat cardiomyocytes overexpressing MG53.

[0066] Infect adult rat cardiomyocytes (10 5 cells / well) after 48 hours, use 10 -7 Insulin stimulation of M for 0 minutes, 5 minutes and 10 minutes, and then the cellular protein was extracted for SDS-PAGE-immunoblotting (Western blot), the results showed that overexpression of MG53 completely inhibited the activation of insulin-mediated downstream signals Akt and ERK ( Figure 7 ). Further, MG53 was overexpressed in differentiated C2C12 myotube cells [2% horse serum (Hyclone, USA) induced for 6 days], with 10 -7 After 10 minutes of insulin stimulation of M, Western blot was performed...

Embodiment 4M

[0067] Example 4 MG53 deficiency inhibits obesity induced by high-fat diet

[0068] C57 mice wild-type and MG53 knockout (see "Nature Cell Biology" for the preparation method of MG53 knockout mice, Cai et.al.2009; 11(1):56-64) were divided into normal diet group and high Two groups of fat diet group, 20 mice in each group. The normal group of C57 mouse wild type and MG53 knockout type were given normal growth and breeding feed (the feed was purchased from the Academy of Military Medical Sciences) from the age of 3 weeks; Feed (the feedstuff is purchased from Research Diets, USA), then measure the body weight of the mice every week, and draw the growth curve of the mice ( Figure 10 ). The results showed that for wild-type mice, the body weight increased significantly (from about 35g to about 55g) after being fed with a high-fat diet, while MG53 deficiency had no significant effect on the weight growth of mice under normal diet conditions, but high-fat diet Diet-induced obes...

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Abstract

The invention relates to application of an MG53 gene to treatment of insulin resistance, type II diabetes mellitus and related diseases thereof. By the invention, the mutual relation between the expression of the MG53 gene and the insulin resistance characteristics is determined; under the condition of the insulin resistance, the expression of the MG53 is obviously raised; the over expression of the MG53 can cause the generation of the insulin resistance; and the defect of the MG53 obviously inhibits all diseases induced by high fat diets, promotes the glucose metabolism, and enhances the insulin sensitivity. Therefore, the MG53 gene can be used as a medical target and used for screening medicines for preventing, relieving and / or treating the insulin resistance, the type II diabetes mellitus and the related diseases thereof. The MG53 gene can also be used as a target gene in the gene treatment and used for designing and preparing the medicines for preventing, relieving and / or treating the insulin resistance, the type II diabetes mellitus and the related diseases thereof and / or chemical reagents; and an effective novel approach for the treatment of the insulin resistance, the type II diabetes mellitus and the related diseases thereof is provided.

Description

technical field [0001] The present invention relates to the application of MG53 gene in the treatment of insulin resistance and type II diabetes and its related diseases, especially in the preparation and / or screening of drugs for preventing, alleviating and / or treating insulin resistance and type II diabetes and its related diseases Application belongs to the field of biotechnology. Background technique [0002] Due to the improvement of people's living standards in my country, the adjustment of diet structure and the change of lifestyle in recent years, the prevalence of diabetes has been increasing, and China has become the second largest country with diabetes after India (1). Type II diabetes accounts for the majority (95%) of diabetic patients, and is closely related to general obesity and / or abnormal body fat distribution (abdominal obesity). [0003] With the development of science and technology, people have realized that insulin resistance is the main feature and c...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61P3/04A61P3/06A61P3/10A61P5/50A61P9/12C12Q1/68
Inventor 肖瑞平曹春梅张岩宋瑞生
Owner BOYA PHARMA
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