Application of nucleolin in preparation of drugs for improving glucose metabolism disorders

A technology for nucleolin and glucose metabolism, which is applied in the field of biomedicine to achieve the effects of enhancing glucose tolerance and insulin sensitivity, improving glucose metabolism disorders, and delaying the progression of the disease.

Active Publication Date: 2019-08-30
SHANDONG PROVINCIAL HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In the prior art, the main research on nucleolin is focused on its mechanism of action to inhibit the proliferation of tumor cells (such as intestinal cancer, gastric cancer, etc.), the mechanism of action to inhibit the apoptosis of cardiomyocytes in diabetic cardiomyopathy, etc. So far, there is no research report on the mechanism of nucleolin in improving the body's glucose metabolism disorder, regulating the activity of glycogen synthase, and regulating the phosphorylation level of glycogen synthase

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  • Application of nucleolin in preparation of drugs for improving glucose metabolism disorders
  • Application of nucleolin in preparation of drugs for improving glucose metabolism disorders
  • Application of nucleolin in preparation of drugs for improving glucose metabolism disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Effect of Nucleolin on Body's Glucose Metabolism Function

[0047] Take 30 6-week-old male C57BL / 6J mice and divide them into the experimental group and the control group on average. The experimental group is fed with a 60% high-fat diet, and the control group is fed with a normal diet to establish a high-fat diet-induced glucose metabolism disorder model. To simulate the early pathological changes of type 2 diabetes. The weekly body weights of the two groups of mice were recorded, and the appetite behavior, feces, and hair of the two groups of mice were observed, and they were killed after 28 weeks. The nucleolin expression level in the liver of group mice, the aminoacid sequence of the nucleolin of described mouse is as shown in SEQ ID No.4, and the obtained result is as follows figure 1 shown.

[0048] Depend on figure 1 A. figure 1 B can be obtained, compared with the control group mice with normal diet, the mice in the experimental group with high-fat...

Embodiment 2

[0050] Example 2 Effect of nucleolin on liver glucose metabolism function

[0051] Take 30 8-week-old male C57BL / 6J mice and divide them into the experimental group and the control group on average. group was injected with empty virus (subsequently referred to as Ncon control group), and the infection units of each group of virus were 3.0*10 8 pfu, to construct a nucleolin overexpression mouse model, such as figure 2 As shown in A. The mice in the two groups were injected once every 6 days, and sacrificed after 6 injections. Before the sacrifice, they were fasted without water. Small animal in vivo imaging technology was used to perform in vivo imaging before the mice were sacrificed. The expression level of nucleolin gene in different tissues and organs of the two groups of mice was detected by tissue quantitative PCR technology, and the protein expression level of nucleolin was detected by western blotting , comparing the expression of nucleolin in different tissues and ...

Embodiment 3

[0054] Example 3 Effect of nucleolin on the body's ability to tolerate glucose and insulin

[0055] With the Ad-NCL experimental group and the Ncon control group in embodiment 2, respectively under normal diet (CD) and high-fat diet (HFD) conditions, by intraperitoneal glucose tolerance (IPGTT) test and intraperitoneal insulin tolerance (IPITT) test, detect the tolerance ability of glucose and insulin of each group of mice, to confirm the regulation effect of nucleolin on glucose metabolism in mouse liver.

[0056] Among them, the processing method of the IPGTT test is: mice are starved for 18 hours and injected with glucose intraperitoneally, the injection dose is 2g glucose / kg mouse body weight, and the blood glucose level of the tail tip of the mice is measured every 30 minutes for a total of 120 minutes to confirm the presence of nucleolin. Role in insulin resistance. The processing method of the IPITT test is: mice are starved for 4 hours and injected intraperitoneally w...

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Abstract

The invention provides an application of nucleolin in the preparation of drugs for improving glucose metabolism disorders, regulating the activity of glycogen synthase and regulating the phosphorylation level of glycogen synthase. According to the invention, it is confirmed that nucleolin is a glucose metabolism-related molecule by establishing a model of high fat diet-induced glucose metabolism disorders and a mouse model of nucleolin overexpression, and it is found that nucleolin can improve the activity of glycogen synthase by inhibiting phosphorylation of glycogen synthase in the liver, thereby improving glycogen synthesis ability of liver tissues, enhancing glucose tolerance dose and insulin sensitivity of the body and participating in the regulation of body glucose homeostasis and the treatment of glucose metabolism disorders; and the up-regulation of nucleolin expression has an effect of resisting abnormal glucose metabolism and insulin resistance. The invention provides a new target for the prevention and treatment of type 2 diabetes mellitus and prediabetes, and nucleolin can be used for studies on the preparation of drugs for early intervention of type 2 diabetes mellitusand delaying the progress of the course of disease.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of nucleolin in the preparation of drugs for improving glucose metabolism disorders. Background technique [0002] In 2017, there were more than 450 million diabetics in the world, and the incidence of diabetes in China was as high as 10.9%, with 114 million patients, ranking first in the world. Metabolic syndrome is often characterized by the coexistence of non-alcoholic fatty liver, hyperlipidemia, and hyperglycemia. According to the National Health and Nutrition Examination Survey (NHANES 1999-2000), more than half of diabetic patients are accompanied by dyslipidemia, and about 61.6% were accompanied by increased triglycerides, and 63.7% were accompanied by decreased high-density lipoprotein cholesterol. At the same time, about 70% of non-alcoholic fatty liver patients will be accompanied by symptoms of glucose metabolism disorders such as insulin resistance or hype...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K45/00A61P3/10A61P5/50
CPCA61K38/1709A61K45/00A61P3/10A61P5/50
Inventor 高聆薄涛姚振宇
Owner SHANDONG PROVINCIAL HOSPITAL
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