Method for promoting expression of insulin receptor substrate-2

a technology of insulin receptor and substrate, which is applied in the direction of drug composition, peptide/protein ingredient, metabolic disorder, etc., can solve the problems of serious diabetic complications, serious human health harm, and impact on the quality of life of patients, so as to reduce the apoptosis of pancreatic islet cells, reduce inflammation, and reduce the damage to the pancreas.

Inactive Publication Date: 2019-10-10
TALENGEN INTERNATIONAL LIMITED
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  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0037]The present invention discovers that plasminogen can alleviate the pancreatic tissue injury, control inflammation, reduce pancreatic islet β cell apoptosis, repair pancreatic tissue, restore the secretion functi

Problems solved by technology

Diabetes mellitus is one of the major diseases that seriously endanger human health.
The main manifestations of diabetes mellitus are abnormal glucose metabolism and metabolic disorders of substances such as fats and proteins; furthermore, long-term hyperglycemia may lead to serious diabetic complications, including microvascular complications, diabetic nephropathy, diabetic cardiomyopathy, diabetic neuropathy, diabetic dermopathy, diabetes mellitus with infections, etc.
Among them, diabetic nephropathy and diabetic neuropathy have a great impact on the quality of the life of patients, and are severely harmful.
Accordingly, in order to achieve the normal blood glucose level, the body will excessively secrete insulin to alleviate the “low-efficiency” state of insulin in service, and if it continues this way, the requirements for the pancreatic islet β cells are getting higher and higher, ultimately causing damage to the pancreatic islet β cells themselves due to “overwork”, thus developing into absolute insulin deficiency.
Studies have shown that long-term high-fat diets lead to pancreatic islet β cell dysfunction, because high-fat diets not only trigger peripheral insulin resistance, but also increase the abdominal fat content and reduce the capacity of insulin to inhibit lipolysis, thereby promoting an increase in the content of free fatty acids, which in turn inhibits the phosphorylation of tyrosine sites in the insulin receptor and the insulin receptor substrates IRS-1 and 1RS-2, thereby inhibiting the activity of P13K, which results in the insulin signal transduction pathway being hindered, thereby forming insulin resistance.
In case of metabolic disorders in an body, such an equilibrium in the body is broken, causing imbalance of the immune system, triggering an inflammatory signal transduction pathway, thereby prompting the body to release a series of inflammatory factors.
Due to genetic or dietary reasons, patients with T2DM are susceptible to insulin resistance; furthermore, in case of patients with elevated blood glucose, hyperglycemia can promote production of IL-6 which can not only reduce expression of GLUT4, reduce transport of glucose by fat cells, hinder glycogen synthesis, and reduce insulin sensitivity, but can also promote secretion of IL-6 by pancreatic islet cells, causing a vicious circle.
Hyperglycemia induces the production of a large amount of IL-1β, which results in pancreatic islet cell apoptosis by activating pathways such as NF-κB, MAPK, Fas and NO, and there are cross-facilitations of various inflammatory pathways to aggravate the apoptosis of pancreatic islet cells, which eventually leads to pancreatic islet function failure [13].
Oxidative stress refers to the imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen spec

Method used

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  • Method for promoting expression of insulin receptor substrate-2
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  • Method for promoting expression of insulin receptor substrate-2

Examples

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example 1

en Promotes Expression of Insulin Receptor Substrate 2 (IRS-2) in Pancreatic Islet of 18-Week-Old Diabetic Mice

[0203]Seven male db / db mice and three male db / m mice, 18 weeks old, were weighed and the db / db mice were randomly divided, according to body weight, into two groups, a group of 3 mice administered with plasminogen and a control group of 4 mice administered with vehicle PBS, on the day the experiment started that was recorded as day 0; in addition, the db / m mice were used as a normal control group. Starting from day 1, plasminogen or PBS was administered. The mice in the group administered with plasminogen were injected with human plasminogen at a dose of 2 mg / 0.2 mL / mouse / day via the tail vein, and the mice in the control group administered with vehicle PBS were injected with an equal volume of PBS via the tail vein, both lasting for 35 consecutive days. On day 36, the mice were sacrificed, and the pancreas was taken and fixed in 4% paraformaldehyde. The fixed pancreas tiss...

example 2

en Lowers Blood Glucose in Diabetic Mice

[0206]Eight 24- to 25-week-old male db / db mice were randomly divided into two groups, a group of 5 mice administered with plasminogen, and a control group of 3 mice administered with vehicle PBS. The mice were weighed and grouped on the day when the experiment began, i.e. day 0. Starting from the 1st day, plasminogen or PBS was administered. The group administered with plasminogen was injected with human plasminogen at a dose of 2 mg / 0.2 mL / mouse / day via the tail vein, and the control group administered with vehicle PBS was injected with an equal volume of PBS via the tail vein, both lasting for 31 consecutive days. After fasting for 16 hours on days 10 and 31, blood glucose testing was carried out using a blood glucose test paper (Roche, Mannheim, Germany).

[0207]The results show that the blood glucose level in mice in the group administered with plasminogen was remarkably lower than that in the control group administered with vehicle PBS, and...

example 3

en Lowers Fructosamine Level in Diabetic Mice

[0208]For five 24- to 25-week-old male db / db mice, 50 μl of blood was collected from venous plexus in the eyeballs of each mouse one day before administration, recorded as day 0, for detecting a concentration of serum fructosamine; and starting from day 1, plasminogen is administered for 31 consecutive days. On day 32, blood was taken from the removed eyeballs to detect the concentration of serum fructosamine. The concentration of fructosamine was measured using a fructosamine detection kit (A037-2, Nanjing Jiancheng).

[0209]The concentration of fructosamine reflects the average level of blood glucose within 1 to 3 weeks. The results show that the concentration of serum fructosamine is remarkably decreased after administration of plasminogen, and as compared with that before administration, the statistical difference is extremely significant (FIG. 3). This indicates that plasminogen can effectively reduce blood glucose in diabetic animals....

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Abstract

The present invention relates to a method for promoting expression of insulin receptor substrate-2, comprising administering an effective amount of plasminogen to a subject; furthermore, the present invention relates to a medicament for promoting expression of insulin receptor substrate-2.

Description

TECHNICAL FIELD[0001]The present invention relates to a method for promoting expression of insulin receptor substrate-2, comprising administering an effective amount of plasminogen to a subject; furthermore, the present invention relates to a medicament for promoting expression of insulin receptor substrate-2.BACKGROUND ART[0002]Diabetes mellitus (DM) is a common genetically predisposed abnormal glucose metabolism disease with endocrine disorder, and is caused by absolute or relative insufficient insulin secretion. In 2015, there were 415 million patients with diabetes mellitus worldwide, and the number of patients with diabetes mellitus is expected to reach 642 million by 2040 [1]. Diabetes mellitus is one of the major diseases that seriously endanger human health.[0003]The main manifestations of diabetes mellitus are abnormal glucose metabolism and metabolic disorders of substances such as fats and proteins; furthermore, long-term hyperglycemia may lead to serious diabetic complic...

Claims

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Application Information

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IPC IPC(8): A61K38/48A61P3/10A61K45/06
CPCA61K38/484C12Y304/21007A61P3/10A61K45/06A61P3/04A61K38/48A61K38/43A61P5/50
Inventor LI, JINAN
Owner TALENGEN INTERNATIONAL LIMITED
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