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Application of metrnl protein in preparing hypolipidemic, hypoglycemic medicine

a technology of metrnl protein and lipidemic medicine, applied in the field of medicine, can solve the problems of chronic damage and dysfunction of various tissues, eye, kidney, heart, etc., and achieve the effects of preventing the increase of blood glucose, preventing the increase of blood lipids, and little side effects

Inactive Publication Date: 2016-09-01
MIAO CHAOYU +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a new application of a protein called Metrnl in the preparation of hypoglycemic and hypolipidemic medicines. The protein prevents the rise of blood glucose and lipid levels in response to intraperitoneal injection of glucose and oral high lipid food, respectively. The invention is based on the discovery of an intraperitoneal injection glucose tolerance test which revealed that the blood glucose level was significantly lower in mice that overexpress Metrnl in adipose tissue compared to control mice, indicating that the protein has a hypoglycemic function. The use of Metrnl protein as a potential hypoglycemic medicine has important significance in the treatment of diabetes, while its use as a hypolipidemic medicine has potential significance in the treatment of hyperlipidemia. Furthermore, the information collected to date suggests that the protein is a safe pharmaceutical with minimal side effects to humans.

Problems solved by technology

The high blood glucose in diabetes results in chronic damage and dysfunction to various tissues, especially eye, kidney, heart, blood vessel and nerve.

Method used

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  • Application of metrnl protein in preparing hypolipidemic, hypoglycemic medicine

Examples

Experimental program
Comparison scheme
Effect test

embodiment 1

Preparation of Metrnl Adipose-Specific Overexpression Mice

[0035]A plasmid containing Fabp4-Metrnl was constructed with the promoter region of Fabp4 and open reading frame of Metrnl. After the verification with sequencing and linearization with restriction enzyme cutting, this plasmid was injected into fertilized eggs which were transplanted into the uterus of pseudopregnant mice. After genomic identification of the offspring, the mice carrying the Fabp4-Metrnl in genome were chosen to mate with C57BL / 6 mice. The next-generation mice carrying the Fabp4-Metrnl in genome were selected into experimental group, and the mice without Fabp4-Metrnl in genome were selected into control group.

[0036]Plasmid containing Fabp4-Metrnl can also be produced using purchased commodities, for example, open reading frame of Metrnl can be purchased from Thermo (Lot. MMM1013-202763251), and the promoter region of Fabp4 can be obtained from Addgene (No. 11424).

[0037]The Metrnl adipose-specific overexpressio...

embodiment 2

Metrnl Overexpression can Prevent the Increase of Blood Glucose Induced by Intraperitoneal Injection of Glucose

[0038]Mice aged 22 weeks have been fed for 16 weeks with high fat diet (Research Diets, Lot. D12492). Both control wild type and Metrnl adipose-specific overexpression mice were administrated with the same dose of glucose via intraperitoneal injection. Follows are the details.

[0039]Mice aged 22 weeks fasted for 8 hours, and were intraperitoneally injected with glucose at a dose of 1 g / kg. Then, blood glucose was detected at different time points (Table 1) with a one touch ultra glucometer (Johnson & Johnson) via tail vein bleeding.

[0040]The results showed that the blood glucose was dramatically lower in Metrnl adipose-specific overexpression mice than that in control wild type mice (Table 1 and FIG. 1).

TABLE 1Adipose-specific overexpression of Metrnl reduces the basal level of bloodglucose and inhibits the rise of blood glucose induced by intraperitoneal injection ofglucose...

embodiment 3

Metrnl Overexpression can Prevent Hyperlipemia Induced by Gavage with Lipid

[0041]Both control wild type mice and Metrnl adipose-specific overexpression mice aged 12 weeks were administrated with triglyceride by gavage. Follows are the details.

[0042]12-week-old mice fasted for 3 hours, and were administrated with fat emulsion (Lipofundin, B. Braun Melsungen) at a dose of 10 μl / g. Blood samples were obtained from the tail vein at different time points. And 10 μl serum was used to detect the concentration of triglyceride with Triglyceride Colorimetric Assay Kit (E1003, Applygen Technologies Inc.)

[0043]The results showed that the blood triglyceride was significantly lower in Metrnl adipose-specific overexpression mice than that in control wild type mice (Table 2 and FIG. 2).

TABLE 2Adipose-specific overexpression of Metrnl reduces the basal levelof blood triglyceride and prevents the increase of blood triglycerideinduced by gavage with fat emulsionReductionof bloodtriglyceride inSerum tr...

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Abstract

The present invention provides an application of Metrnl protein in preparing a hypolipidemic, hypoglycemic medicine or dietary supplement. The present invention further provides a method for preparing a mouse with fat-specific overexpression of Metrnl.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of PCT application No. PCT / CN2014 / 000949, which was filed on Oct. 27, 2014 based on Chinese Patent Application No. 201310525181.5 filed on Oct. 29, 2013 and Chinese Patent Application No 201310525184.9 filed on Oct. 29, 2013, the contents of which are incorporated herein by reference.TECHNICAL FIELD[0002]The present invention relates to the field of medicine, specifically, application of metrnl protein in preparing hypolipidemic, hypoglycemic medicine.BACKGROUND ART[0003]METRNL is a novel protein encoded by gene Metrnl, with a molecular weight about 30 kDa. The amino acid sequence of human METRNL was displayed in protein database of National Center for Biotechnology Information with sequence number NP_001004431.1. The tissue expression pattern and functions of Metrnl were seldom researched.[0004]China Application of application No. CN200980137344.4 named “Therapeutic use of a growth factor METRNL” with P...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K14/475
CPCC07K14/475A23V2002/00A61K39/00A23L1/305A23L33/17A61K38/19A61K38/22A61P3/06A61P3/10C07K14/52
Inventor MIAO, CHAOYULI, ZHIYONGWANG, PEI
Owner MIAO CHAOYU