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Function and application of three-structural-domain protein 8 in treating non-alcoholic fatty liver disease and II type diabetes mellitus

A fatty liver and diabetes technology, applied in gene therapy, medical preparations containing active ingredients, metabolic diseases, etc., can solve problems such as efficacy and safety that need further clinical verification.

Inactive Publication Date: 2017-03-15
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, some new diabetes drugs designed based on these new targets have been marketed and have achieved good hypoglycemic effects, such as GLP-1 receptor agonists, DPP-4 inhibitors and SGLT-2 inhibitors, etc., but most of them are still It is in the stage of clinical or preclinical research, and its efficacy and safety need further clinical verification

Method used

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  • Function and application of three-structural-domain protein 8 in treating non-alcoholic fatty liver disease and II type diabetes mellitus
  • Function and application of three-structural-domain protein 8 in treating non-alcoholic fatty liver disease and II type diabetes mellitus
  • Function and application of three-structural-domain protein 8 in treating non-alcoholic fatty liver disease and II type diabetes mellitus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] [Example 1] Fatty liver in mice and type Ⅱ diabetes model (diet induced obesity, DIO) were obtained

[0057] (1) Grouping of experimental animals: 8-week-old, male, WT mice and TRIM8-KO mice were selected and given two special diets, D12942 high-fat diet (High fat diet, HFD) and D12450B low-fat diet (Normal chow , NC) feeding, that is, WT NC group, KO NC group, WT HFD group, KO HFD group, a total of 4 groups.

[0058] (2) The model induces the operation process through high-fat feed:

[0059] Using WT and KO mice, the DIO model was established, and phenotype correlation analysis was performed to clarify the role of XX gene on fatty liver and type Ⅱ diabetes. 8-week-old, male, WT mice and XX-KO (TG) mice were selected and fed with two special diets, D12942 high-fat diet (Highfat diet, HFD) and D12450B low-fat diet (Normal chow, NC), respectively. That is WT NC group, KO NC group, WT HFD group, KO HFD group, a total of 4 groups. The food intake of the mice was recorded...

Embodiment 2

[0060] [Example 2] Determination of mouse fasting body weight, blood sugar level and serum insulin level

[0061] (1) Detection of fasting body weight of mice

[0062] ①Fasting: fast the mice to be tested at 8:00 am (without water), and start the experimental operation at 2:00 pm.

[0063] ② Weighing: Weigh at 0 week, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks respectively. In a small bucket, measure the weight and record the data. Feed amount detection: After the weighing operation is completed, add feed to the mice, and record the amount of feed for the mice on the dynamic electronic balance.

[0064] (2) Fasting blood glucose level detection experiment

[0065] All the mice to be tested were fasted from 8:00 am to 2:00 pm (without water), that is, the experimental operation was started after 6 hours of fasting.

[0066] ① Blood glucose meter preparation: Check the battery of the blood glucose meter (Johnson & Johnson, ONETOUCH, USA), press the switch on ...

Embodiment 3

[0090] [Example 3] Glucose tolerance test (intraperitoneal glucose tolerance test, IPGTT)

[0091] In the 12th week of the experiment, the intraperitoneal glucose injection test (IPGTT) was performed to evaluate the glucose tolerance of the mice.

[0092] (1) Before measuring blood glucose, measure the fasting body weight of the mice, and calculate the injection volume of glucose based on 10 μL / g.

[0093] (2) First detect the fasting blood glucose at 0 minutes before the glucose injection, and inject the glucose solution intraperitoneally quickly after the detection is completed.

[0094] (3) Operation method of intraperitoneal injection: ①Fix the mouse; grab the mouse, grab the tail of the mouse with the little finger and ring finger of the left hand, and grab the neck of the mouse with the other three fingers, so that the head of the mouse is downward, and the The abdomen of the mouse is fully exposed. ②Needle positioning and injection: insert the needle from the side of ...

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Abstract

The invention discloses the function and application of three-structural-domain protein 8 in treating non-alcoholic fatty liver disease and II type diabetes mellitus. TRIM8 gene knockout mice and wild type C57 mice are used as experimental subjects, by means of a high-fat diet induced fat mice model, the result indicates that compared with the wild type C57 mice, the weight of the TRIM8 gene knockout mice is reduced, the fasting blood-glucose level of the TRIM8 gene knockout mice is lower than that of control group WT mice, and hepatosis is obviously relieved. Mouse liver weight, the liver / weight ratio and a lipid component pathological staining result show that fatty liver pathological changes of the TRIM8-KO mice having high-fat diet are obviously relieved, and lipid accumulation is remarkably reduced. Therefore, TRIM8 can serve as a drug target for screening and treating fatty liver disease and / or II type diabetes mellitus, and inhibitor of TRIM8 can be used for preparing a drug for treating fatty liver disease and / or II type diabetes mellitus.

Description

technical field [0001] The invention belongs to the field of gene function and application, in particular to a triple domain protein 8 gene (Thetripartite motif proteins, TRIM8) used as a drug target in the screening of drugs for preventing, alleviating and / or treating fatty liver and / or type 2 diabetes application. Background technique [0002] Non-alcoholic fatty liver disease (NAFLD) refers to a clinicopathological syndrome characterized by diffuse hepatic steatosis and lipid accumulation in addition to alcohol and other definite liver damage factors. Disease spectrum includes nonalcoholic simple fatty liver, nonalcoholic steatohepatitis and its associated cirrhosis, and hepatocellular carcinoma [1-2] . With the improvement of living standards and changes in diet structure, the incidence of NAFLD has increased year by year, and it has become the second largest chronic liver disease after viral hepatitis in my country. Type 2 diabetes mellitus (T2DM), also known as non-...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68A61K48/00A61K45/00A61K39/395A61P1/16A61P3/10
CPCC12Q1/6883A61K31/7088A61K39/395A61K45/00C12Q2600/136C12Q2600/158
Inventor 李红良黄赞
Owner WUHAN UNIV
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