Application of a kind of gp73 inhibitor in preparing medicine for treating diabetes

A diabetes and inhibitor technology, applied in the application field of medicine, can solve the problem that the biological function of GP73 is not very clear, and achieve the effect of enhancing the function of raising blood sugar and gluconeogenesis, and prolonging the half-life

Active Publication Date: 2022-08-02
BEIJING SUNGEN BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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 a kind of gp73 inhibitor in preparing medicine for treating diabetes
  • Application of a kind of gp73 inhibitor in preparing medicine for treating diabetes
  • Application of a kind of gp73 inhibitor in preparing medicine for treating diabetes

Examples

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Comparison scheme
Effect test

Embodiment 1

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

[0112] Experimental methods: In order to compare whether there is a difference in the level of soluble GP73 in serum between diabetic and healthy people, we conducted 75 healthy physical examinations in outpatient physical examinations in multiple physical examination centers and 190 diabetic patients diagnosed with diabetes by endocrinology department. Serum soluble GP73 levels were detected after overnight fasting. These enrolled populations, matched for sex and age, did not differ significantly between healthy and diabetic populations (eg Figure 1A shown).

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

Embodiment 2

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

[0115] Experimental method: First, the GP73 protein was expressed and purified by the mammalian cell expression system HEK293 cells, and the recombinant mouse soluble GP73 protein (rmsGP73) was obtained (NCBI Reference Sequence: NP_001030294.1). This protein is missing amino acids 1-55 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 examples of the present invention are all this recombinant mouse soluble GP73 protein, referred to as rmsGP73). We used 300ng / dose of rmsGP73 and PBS to inject C57BL / 6N mice (ie, the experimental group and the PBS control group, 10 mice in each group) through the tail vein, respectively, and detected 24 hours and 48 hours after injection. Fasting blood glucose (blood glucose meter and blood glucose test strips were purchased from Roche), and intraperitoneal glucose tolerance (IPGTT), ...

Embodiment 3

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

[0118] Experimental method: The fluorescent dye Cy7 control group and Cy7-labeled rmsGP73 protein (rmsGP73-Cy7) experimental group were intravenously injected into mice to detect the fluorescence distribution and fluorescence intensity according to the detection method or part 5 of the experimental method.

[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 (e.g. Figure 3A). After taking its organs, it was found that compared with the Cy7 control group, the fluorescence intensity of rmsGP73-Cy7 in the liver and kidney was the strongest (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 of the Cy7 control gr...

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Abstract

The embodiment of the present invention relates to the application of a GP73 inhibitor in the preparation of a medicine for treating diabetes. In the examples of the present invention, the inventors found that GP73 plays a key role in blood sugar regulation. In particular, it has been found that soluble GP73 can specifically bind to glucagon to form a complex, and enhance the blood sugar-raising function and gluconeogenesis function of glucagon. , prolong the half-life of glucagon; found that soluble GP73 can activate liver and / or kidney glucose production and gluconeogenesis signaling pathway in a glucagon-independent manner; based on the above findings of GP73 regulation of blood sugar, The inventors have also proved through animal experiments that GP73 inhibitors can reduce the blood sugar level and the glycosylated hemoglobin level of diabetic mice, and have a protective effect on pancreatic islet beta cells, thereby having the effect of treating diabetes.

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 a medicine for treating diabetes. Background technique [0002] According to estimates by the International Diabetes Federation, the global prevalence of diabetes among adults aged 20 to 79 in 2017 was about 8.8%, with about 425 million people, of which 4 million died of diabetes, accounting for 10.7% of the total global deaths. As the world's largest diabetes country, China has about 114.4 million patients. This number is increasing year by year, and it is estimated that by 2045, there will be at least 629 million people in the world with diabetes between the ages of 20 and 79. [0003] Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which is mainly divided into four categories: type I diabetes, type II diabetes, gestational diabetes and other special types of diabetes. Type Ⅰ diabetes is insulin-depe...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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