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Application of GP73 inhibitor in preparation of medicine for treating diabetes

A diabetes and inhibitor technology, applied in the application field of medicine, can solve the problems such as the unclear biological function of GP73, achieve the effect of enhancing blood sugar raising function and gluconeogenesis function, and prolonging the half-life

Active Publication Date: 2021-09-24
BEIJING SUNGEN BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Although the abnormally high expression of GP73 is closely related to a variety of tumors, the biological function of GP73 is still not very clear
The extracellular function of soluble GP73 is poorly understood, with only one report showing that GP73 in serum mediates the transmission of endoplasmic reticulum stress between hepatocytes and immune cells, and this cascade effect induces tumor Recruitment of macrophages creates immune tolerance in the tumor microenvironment

Method used

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  • Application of GP73 inhibitor in preparation of medicine for treating diabetes
  • Application of GP73 inhibitor in preparation of medicine for treating diabetes
  • Application of GP73 inhibitor in preparation of medicine for treating diabetes

Examples

Experimental program
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Effect test

Embodiment 1

[0111] Example 1. The level of soluble GP73 in the serum of diabetic population was significantly higher than that of healthy physical examination population

[0112] Experimental method: In order to compare whether the level of soluble GP73 in serum is different between diabetics and healthy people, we conducted 75 cases of healthy people who underwent physical examination in multiple physical examination centers and 190 cases of diabetic patients diagnosed as diabetes by the Department of Endocrinology. The level of serum soluble GP73 was detected after overnight fasting. These enrolled populations were matched for sex and age, and their distribution was not significantly different between healthy and diabetic populations (such as Figure 1A shown).

[0113] Experimental results: in healthy people, the average serum concentration of soluble GP73 is 52.81ng / ml (3.5-146ng / ml); in diabetic people, the average serum concentration of soluble GP73 is 68.82ng / ml (19.36-198ng / ml), ...

Embodiment 2

[0114] Example 2. Recombinant soluble GP73 regulates glucose metabolism

[0115] Experimental method: Firstly, GP73 protein was expressed and purified by HEK293 cells, a mammalian cell expression system, to obtain genetically recombinant mouse soluble GP73 protein (rmsGP73) (NCBI Reference Sequence: NP_001030294.1). This protein lacks the 1-55 amino acids of GP73, and is the main form of soluble GP73 in blood (the recombinant soluble GP73 proteins used in the mouse experiments involved in the embodiments of the present invention are all recombinant mouse soluble GP73 proteins, referred to as rmsGP73). After injecting C57BL / 6N mice (experimental group and PBS control group, 10 mice in each group) through the tail vein with 300ng / mouse rmsGP73 and PBS, we detected the expression of mice 24 hours and 48 hours after injection. Fasting blood glucose (glucose meter and blood glucose test strips were purchased from Roche), and intraperitoneal glucose tolerance (IPGTT), pyruvate tole...

Embodiment 3

[0117] Example 3. Recombinant soluble GP73 accumulates in mouse liver and kidney

[0118] Experimental method: According to the detection method or the fifth part of the experimental method, the fluorescent dye Cy7 control group and the Cy7-labeled rmsGP73 protein (rmsGP73-Cy7) experimental group were injected intravenously into the mice for fluorescence distribution and fluorescence intensity detection.

[0119] Experimental results: In vivo imaging of mice showed that compared with the Cy7 control group, rmsGP73-Cy7 mainly accumulated in the liver and kidney (such as Figure 3A). After taking its organs, it was found that compared with the Cy7 control group, the fluorescence intensity of rmsGP73-Cy7 was the strongest in the liver and kidney (such as Figure 3B ). The fluorescence intensity of each organ of the mouse was analyzed and processed, and it was found that the fluorescence intensity of the liver, kidney, and spleen of rmsGP73-Cy7 was significantly higher than that...

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Abstract

The embodiment of the invention relates to application of a GP73 inhibitor in preparation of medicine for treating diabetes. According to the embodiment of the invention, the inventor finds that GP73 plays a key role in blood glucose regulation, and particularly finds that soluble GP73 can be specifically combined with glucagon to form a compound, the blood glucose increasing function and the gluconeogenesis function of the glucagon are enhanced, and the half-life period of the glucagon is prolonged; the condition that soluble GP73 can activate generation of liver and / or kidney sugar and a gluconeogenesis signal channel in a manner of not depending on glucagon is found; and based on the found regulation effect of GP73 on blood glucose, the inventor also proves that the GP73 inhibitor can reduce the blood glucose level and glycosylated hemoglobin level of diabetic mice, has a protection effect on pancreas islet beta cells, and achieve an effect of treating diabetes through animal experiments.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of a GP73 inhibitor in the preparation of medicines for treating diabetes. Background technique [0002] According to the estimates of the International Diabetes Federation, in 2017, the global prevalence of diabetes among adults aged 20-79 was about 8.8%, and there were about 425 million people. Among them, 4 million people died of diabetes, accounting for 10.7% of the total global deaths. China is a big diabetes country in the world, with about 114.4 million people suffering from diabetes. This number is increasing year by year. It is estimated that by 2045, there will be at least 629 million people in the world with diabetes aged 20-79. [0003] Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which is mainly divided into four types: type 1 diabetes, type 2 diabetes, gestational diabetes and other special types of diabetes. Type Ⅰ diabetes i...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61P3/10A61P5/48A61P9/10A61P13/12A61P15/00A61P27/02A61P27/12G01N33/74
CPCA61K45/00A61P3/10A61P15/00A61P13/12A61P27/02A61P9/10A61P27/12A61P5/48G01N33/74G01N2333/605G01N2800/042C12N15/113C07K16/30C07K2317/76C07K16/18A61K2039/505A61K2039/545G01N2500/02C12N2310/14A61K45/06A61K31/713A61K31/7105A61K31/155A61K38/26A61K38/28A61K39/3955C07K16/28C12N15/1138
Inventor 林长青孙志伟高琦郄霜徐磊李靖林建波朱恒奇郑飞刘雪超
Owner BEIJING SUNGEN BIOMEDICAL TECH CO LTD
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