CN111450253A

CN111450253A - Medicine for preventing/treating type 2 diabetes and application

Info

Publication number: CN111450253A
Application number: CN202010226531.8A
Authority: CN
Inventors: 阮庆国; 刘芮伶; 贺晓珍; 刘翠莲; 杨浩然
Original assignee: Shenzhen Institute of Advanced Technology of CAS
Current assignee: Shenzhen Institute of Advanced Technology of CAS
Priority date: 2020-03-27
Filing date: 2020-03-27
Publication date: 2020-07-28

Abstract

The application provides a medicine for preventing/treating type 2 diabetes and application thereof, wherein an active component in the medicine takes miR-21 as a target spot, and miR-21 is promoted in a targeted manner. Through the mode, the application can promote the function of the pancreatic island to achieve the purpose of reducing blood sugar.

Description

Medicine for preventing/treating type 2 diabetes and application

Technical Field

The application relates to the technical field of medicines, in particular to a medicine for preventing/treating type 2 diabetes and application thereof.

Background

At present, about 90 percent of patients with diabetes mellitus belong to type 2 diabetes mellitus T2DM, and the remarkable pathophysiological characteristics of the diabetes mellitus T2DM are that the reduction of the glucose metabolism regulation capacity of insulin (insulin resistance) is accompanied by the reduction (or relative reduction) of insulin secretion caused by the functional defect of insulin β cells, the abnormal function of the insulin β cells is a key factor which causes the abnormal glucose tolerance of people with normal glucose metabolism and the development of the abnormal glucose tolerance group into T2DM, and is also a key factor of the gradual progress and deterioration of the disease condition of the patients with T2 DM.

The current ways for treating T2DM comprise blood sugar reducing drug therapy, metabolic surgery therapy and islet transplantation value, wherein the blood sugar reducing drug comprises sulfonylureas, meglitinides, G L P-1 receptor agonists, DPP-4 inhibitors, biguanides, thiazolidinediones, direct injection of insulin and the like, the blood sugar reducing drug therapy mainly controls the blood sugar level of a patient, long-term insistence is needed, the life quality of the patient is influenced, the blood sugar control method can cause that the insulin release is not regulated by blood sugar, or the blood sugar release does not accord with physiological rhythm and the like, the blood sugar of the patient often fluctuates greatly and easily causes large adverse drug reactions such as hypoglycemia syncope and the like, the metabolic surgery needs multi-discipline cooperation, the whole course management before, during surgery and after surgery is carried out, individual differences exist in curative effect, the control of effectiveness and safety of the surgery is carried out, the islet transplantation can delay the dependence of the patient on insulin injection, but cannot fundamentally solve the antibody of islet cells, the rejection of the organism and the toxic effect of immunosuppressive agent on β cells, and the low survival rate of the islet transplantation side effect and high survival rate of the islet transplantation cost.

Therefore, there is a need to develop a novel hypoglycemic agent, which provides a new means and strategy for clinical prevention and treatment of type 2 diabetes.

Disclosure of Invention

The application mainly solves the technical problem of providing a medicament for preventing/treating type 2 diabetes and application thereof, and can achieve the purpose of reducing blood sugar by promoting the function of pancreatic islets by taking miR-21 as a target point.

In order to solve the problems, the application provides a medicament for preventing/treating type 2 diabetes, wherein an active ingredient in the medicament takes miR-21 as a target point and promotes miR-21 in a targeted manner.

Wherein the active component of the medicament comprises an agonist of miR-21.

Wherein the active component of the medicament comprises a mimic of miR-21.

Wherein the active component of the medicament comprises an analogue of miR-21.

Wherein, the gene sequence in the active component of the medicine comprises:

5'-UAGCUUAUCAGACUGAUGUUGA-3' as sense strand;

antisense strand 3 '-AUCGAAUAGUCUGACUACAACU-5'.

Wherein, still include: a pharmaceutically acceptable carrier for said active ingredient.

In order to solve the problems, the second aspect of the application provides application of an agonist of miR-21 in preparation of a medicine for preventing/treating type 2 diabetes.

Wherein, the gene sequence of the agonist of the miR-21 comprises:

5'-UAGCUUAUCAGACUGAUGUUGA-3' as sense strand;

antisense strand 3 '-AUCGAAUAGUCUGACUACAACU-5'.

In order to solve the problems, the third aspect of the application provides application of the miR-21 mimic in preparation of a medicine for preventing/treating type 2 diabetes.

In order to solve the problems, the fourth aspect of the application provides application of the miR-21 analogue in preparation of a medicine for preventing/treating type 2 diabetes.

Compared with the prior art, the active ingredient in the medicine for preventing/treating type 2 diabetes provided by the application takes miR-21 as a target point, and the miR-21 is promoted in a targeted manner, so that the expression of Glut2 in type 2 diabetes pancreatic islets and the production of insulin are increased, and the blood sugar level of the pancreatic islets is remarkably reduced, thereby providing a new means and strategy for clinically preventing and treating type 2 diabetes.

Drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts. Wherein:

FIG. 1a is a schematic of the change in blood glucose over time for 3 week-sized miR-21 β KO and WT mice;

FIG. 1b is a schematic of the change in blood glucose over time for 6 week-sized miR-21 β KO and WT mice;

FIG. 1c is a schematic of the change in blood glucose over time for 7 week-sized miR-21 β KO and WT mice;

FIG. 1d is a schematic of the change in blood glucose over time for 10 week-sized miR-21 β KO and WT mice;

FIG. 1e is a schematic of the change in blood glucose over time for 27 week-sized miR-21 β KO and WT mice;

FIG. 2a is a graph of comparison of serum insulin levels in 8 week-old miR-21 β KO and WT mice;

FIG. 2b is a graph comparing in vitro insulin secretion of 8 week-sized miR-21 β KO and WT mice;

FIG. 3a is a graph showing miR-21 β KO mice and WT mouse-associated Gluts expression levels;

FIG. 3b is a schematic representation of the detection of Glut2 fluorescence in miR-21 β KO and WT mice;

FIG. 3c is a graph showing the statistical results of Glut2 in miR-21 β KO and WT mice;

FIG. 3d is a graph showing the results of the detection of the level of Glut2 protein in miR-21 β KO and WT mice;

FIG. 4a is a schematic of weight control of 7 week-sized WT and miR-21 β KO mice;

FIG. 4b is a schematic of weight control of 27 week-sized WT and miR-21 β KO mice;

FIG. 4c is a schematic of blood glucose control of 7 week old WT and miR-21 β KO mice;

FIG. 4d is a schematic of blood glucose control of 27 week old WT and miR-21 β KO mice;

FIG. 5a is a schematic representation of immunofluorescent staining of 7 week-sized WT and miR-21 β KO mice;

FIG. 5b is a schematic representation of immunofluorescent staining of 27 week-sized WT and miR-21 β KO mice;

FIG. 5c is a graph comparing the number of cells in 7 week-sized WT and miR-21 β KO mice β;

FIG. 5d is a graph comparing the size of WT and miR-21 β KO mouse β cells at 7 weeks of age;

FIG. 5e is a graph comparing the number of 27 week-sized WT and miR-21 β KO mouse β cells;

FIG. 5f is a graph comparing the size of 27 week-sized WT and miR-21 β KO mouse β cells;

FIG. 6a is a detailed process diagram of miR-21 agonist or NC treatment;

FIG. 6b is a schematic of the detection of blood glucose levels at different time points;

FIG. 7a is a graph comparing the expression levels of agonist of miR-21 and Glut2 after NC treatment;

FIG. 7b is a graph comparing the expression levels of Glut2 and protein after agonist and NC treatment of miR-21;

FIG. 7c is a graph comparing agonist and NC treated insulin levels for miR-21;

FIG. 8a is a graph showing the results of measuring body weight at various time points;

FIG. 8b is a graph showing the results of TG, TCHO, HD L-C, L D L-C in the mouse serum after the mice were sacrificed at day 11.

Detailed Description

The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.

Type 2 diabetes T2DM, also known as non-insulin dependent diabetes, is a group of diseases caused by relatively insufficient insulin resistance and insulin secretion. The importance of these two factors varies from patient to patient in the different stages of the disease, from insulin resistance manifested primarily as a relative insufficiency of insulin secretion to insulin resistance manifested primarily as a deficiency of insulin secretion. Insulin resistance initiates the onset of T2DM, but islet function is normal and is otherwise a determinant of whether T2DM occurs.

In order to improve the function of pancreatic islets, the application provides a medicament for preventing/treating type 2 diabetes, wherein the active component in the medicament takes miR-21 as a target point, and the miR-21 is promoted in a targeted manner so as to increase the expression of Glut2 in the pancreatic islets of type 2 diabetes and the production of insulin and obviously reduce the blood sugar level of the pancreatic islets of type 2 diabetes, thereby providing a new means and strategy for clinically preventing and treating type 2 diabetes.

In one embodiment, the active ingredient of the medicament comprises an agonist of miR-21; alternatively, the active ingredient of the medicament comprises a mimetic of miR-21; alternatively, the active ingredient of the medicament comprises an analogue of miR-21. The agonist or the mimic or the analogue of the miR-21 can be synthesized artificially, the effects of the agonist or the mimic or the analogue are that the level of the miR-21 is increased, the agonist or the mimic or the analogue can be combined with the same site, only the form or the modification is different, and the special chemical modification aims to enter the body more easily and is not easy to degrade, so that the agonist or the mimic or the analogue of the miR-21 can play a role in the body stably. Test research shows that the agonist or the simulant or the analog of the miR-21 can quickly reduce the blood sugar of a type 2 diabetes mouse in a test, and provides a new means and strategy for clinically preventing and treating type 2 diabetes; and the agonist or the mimic or the analogue of the miR-21 has small molecular weight, simple structure and convenient administration mode.

Further, the gene sequences in the active ingredients (e.g., agonists or mimetics or analogs of miR-21) of the above-mentioned drugs include:

sense strand 5'-UAGCUUAUCAGACUGAUGUUGA-3' (SEQ ID NO. 1);

3'-AUCGAAUAGUCUGACUACAACU-5' (SEQ ID NO. 2).

In addition, the medicine also comprises a carrier of a pharmaceutically acceptable active component. Such as inert diluents, fillers, water, and the like. The above-mentioned medicament may further comprise additional ingredients, if necessary, such as a flavoring agent, a binder, and the like.

In the present application, the effective dose of the above-mentioned drugs depends on the species, sex, body weight, age, medical condition, administration route of the patient and the severity of the condition to be treated. The skilled practitioner can readily determine and prescribe a pharmaceutically effective dose for the prevention/treatment of the disease.

Of course, in other embodiments, the above-mentioned drugs may also contain other effective ingredients of drugs that help prevent/treat type 2 diabetes. For example, the medicament for preventing/treating type 2 diabetes in this embodiment includes at least two active components, namely a first active component and a second active component, wherein the first active component is an agonist or a mimetic or an analog of the above miR-21, and the second active component is another effective component which helps to prevent/treat type 2 diabetes. In this embodiment, the first active ingredient and the carrier may be formulated into a first formulation using conventional formulation techniques, the second active ingredient and the carrier may be formulated into a second formulation using conventional formulation techniques, and the patient may administer the first formulation and the second formulation sequentially. Alternatively, the first active ingredient, the second active ingredient and the carrier may be formulated by conventional formulation techniques to form a third formulation, which is administered to the patient. In addition, the effective dosage ratio of the first active component and the second active component is 1:1, 2:1, 1:2, etc., and the effective dosage ratio can be adjusted by the physician according to the actual situation, which is not limited in the present application.

The application also provides application of the miR-21 agonist in preparation of a medicine for preventing/treating type 2 diabetes. The miR-21 agonist can increase the level of miR-21, and experimental studies show that the miR-21 agonist can rapidly reduce the blood sugar of mice with type 2 diabetes, and provides a new means and strategy for clinically preventing and treating type 2 diabetes; and the agonist of miR-21 has small molecular weight, simple structure and convenient administration mode. In addition, the agonist of the chemically modified miR-21 has high stability and can play a role stably in vivo.

In this example, the gene sequence of the agonist of miR-21 includes:

5'-UAGCUUAUCAGACUGAUGUUGA-3' as sense strand;

antisense strand 3 '-AUCGAAUAGUCUGACUACAACU-5'.

The application also provides application of the miR-21 mimic in preparation of a medicament for preventing/treating type 2 diabetes. The miR-21 simulant can increase the level of miR-21, and experimental studies show that the miR-21 simulant can rapidly reduce the blood sugar of mice with type 2 diabetes, and provide a new means and strategy for clinically preventing and treating type 2 diabetes; and the miR-21 mimic has small molecular weight, simple structure and convenient administration mode.

The application also provides application of the miR-21 analogue in preparation of a medicine for preventing/treating type 2 diabetes. The miR-21 analogue can increase the level of miR-21, and experimental studies show that the miR-21 analogue can rapidly reduce the blood sugar of mice with type 2 diabetes, and provides a new means and strategy for clinically preventing and treating type 2 diabetes; and the analog of miR-21 has small molecular weight, simple structure and convenient administration mode.

Specific data are provided below to illustrate that agonists or analogues or mimetics of miR-21 provide a useful reference for the prevention/treatment of type 2 diabetes.

The majority of studies at present suggest that insulin resistance is due to a pathological increase in the level of factors in the body that interfere with insulin signaling, studies have found that insulin resistance is related to the number of Insulin Receptors (IR) and their affinity for insulin, i.e. the greater the number of IR or the stronger the affinity the more sensitive a tissue is to insulin, whereas the lesser the number of IR or the weaker the less sensitive a tissue is to insulin, i.e. the tissue is resistant to insulin, clinically it is more common in overweight or obese patients that insulin cannot fully exert its normal physiological effects due to a reduced number of IR or defects in the cell membrane of the patient, resulting in insulin resistance, ultimately resulting in t2dm, whereas insulin is a hormone involved in metabolic regulation that is produced by β cells in response to increased blood glucose, and that long-term chronic hyperglycemia (glucotoxicity) and hyperlipidemia (lipotoxicity) lead to β cell function impairment.

mirnas are a class of single-stranded RNA molecules 21-25 nucleotides in length, originally a class of endogenous non-coding RNAs found in eukaryotes and highly conserved across different species. miRNA is specifically combined with messenger ribonucleic acid (mRNA), thereby inhibiting the expression of transcribed genes and playing an important role in the aspects of regulating and controlling cell cycle, organism development time sequence and the like. Typically, one miRNA can regulate tens or even hundreds of genes, and to date, thousands of human mirnas have been discovered, which were initially estimated to control 50-70% of human gene expression, but only a few of mirnas have been functionally identified. Among them, miR-21 is one of the human miRNAs discovered earlier, and it is used as oncogene to participate in post-transcriptional gene regulation, and plays an important role in cell differentiation, proliferation and apoptosis. miR-21 is closely associated with tumorigenesis, it was originally found to be overexpressed in a range of solid tumors, including breast, lung, colon, stomach and pancreas, and miR-21 is therefore closely associated with tumorigenesis. However, in recent years, there has been no study on miR-21 in type 2 diabetes.

To investigate the role of miR-21 in the regulation of islet function in islet β cells, we constructed 3-week, 6-week, 7-week, 10-week, and 27-week-sized islet β cell-specific knockout miR-21(miR-21 β KO) mice as well as wild-type (WT) mice (i.e., no miR-21 was specifically knocked out in islet β cells).

Please refer to fig. 1a, fig. 1b, fig. 1c, fig. 1d and fig. 1e, wherein fig. 1a is a schematic diagram of the change of blood glucose of miR-21 β KO mice and WT mice in 3 weeks size over time, fig. 1b is a schematic diagram of the change of blood glucose of miR-21 β KO mice and WT mice in 6 weeks size over time, fig. 1c is a schematic diagram of the change of blood glucose of miR-21 β KO mice and WT mice in 7 weeks size over time, fig. 1d is a schematic diagram of the change of blood glucose of miR-21 β KO mice and WT mice in 10 weeks size over time, fig. 1e is a schematic diagram of the change of blood glucose of miR-21-5932 KO mice and WT mice in 27 weeks size over time, it can be seen from the graphs that the 2-hour blood glucose tolerance test results show that the change trend of blood glucose is increased within 0-15 minutes, the decrease to fasting level within 15 minutes-2 hours, the decrease of miR-21 KO within 3 weeks, 6 weeks, 7 weeks, 10 weeks and 27 weeks size over 2-21 minutes shows a significant decrease of miR-387 mice's blood glucose tolerance, and the decrease of miR-21 minutes shows a significant decrease of miR-3-90 minutes.

Further, please refer to fig. 2 a-2 b, fig. 2a is a comparison graph of the serum insulin content in 8-week-sized miR-21 β KO mice and WT mice, and fig. 2b is a comparison graph of the serum insulin content in 8-week-sized miR-21 β KO mice and WT mice in vitro, as can be seen from fig. 2a, mice of about 8 weeks were subjected to an in vivo blood glucose tolerance test, serum was collected for a period of 30 minutes, and E L ISA detected insulin in the serum, and the results showed that the serum insulin content in miR-21 β KO mice was significantly lower than that in the WT group at 30 minutes, as can be seen from fig. 2b, after isolating the insulin of WT and miR-21 β KO mice, stimulation was performed with low-concentration glucose (2.8mM) and high-concentration glucose (16.7mM), respectively, in vitro, and the results showed that there was no significant difference between the insulin secretion in the two groups under low-concentration glucose stimulation, while the insulin secretion in the group under high-concentration glucose stimulation, miR-21 KO 2 mice, i.e., the insulin secretion of the insulin-21 mice was significantly reduced in the gss-21 rs-deficient in the insulin secretion mediated by the miR-21 rs.

In addition, during the process of insulin production by glucose stimulation insulin, the first step is that glucose enters islet β cells through glucose transporters (Gluts), so that the mRNA expression of 5 major Gluts is detected, islets of WT and miR-21 β KO mice are isolated, and the expression levels of 5 Gluts in WT and miR-21 β KO 0 mice are obtained through real-time quantitative PCR detection, specifically referring to FIG. 3a, FIG. 3a is a miR-21 β KO mouse and WT mouse-related Gluts expression level schematic diagram, it can be seen that only the mRNA level of Glut2 in islets of miR- β KO mice is significantly lower than that of WT group, referring to FIG. 3b and FIG. 3c, FIG. 3b is a miR-21 KO 8 mice and a Glut 6 fluorescence detection schematic diagram in WT mice, fig. 3c is a miR-21 KO β KO mice and a WT group, and a miR-27 mice secreting glucose protein, and the results of miR-21 in-598 KO mice and a miR-7 KO mice are significantly lower than that the miR-21 protein secretion statistics result, and miR-11 miR-21 miR-27 secretion of miR-21 mice are significantly lower than that the miR-trypsin secretion protein secretion in miR-5 secretion statistics result of miR-mice, and miR-induced by the miR-21 miR-Pit-21 mice secretion is significantly lower than that the miR-Pit-induced by the miR-Pit protein secretion in the miR-Pit mice secretion statistics result in the miR-Pit mice secretion test result of WT-Pit mice, and miR-Pit mice, which is significantly lower than that the miR-Pit protein secretion results in the miR-Pit mice, and miR-Pit mice secretion results in the miR.

To verify whether increasing miR-21 in the islets could increase glucose-stimulation mediated insulin secretion and lower blood glucose levels, we introduced an agonist of miR-21 into the pancreas of mice using transfection reagents that target the pancreas of mice. The agonist of miR-21 is double-stranded small RNA which is specially marked and chemically modified, and regulates the biological function of a target gene by simulating endogenous miRNA. In this experiment we used db/db mice (type 2 diabetic mouse model) treated every three days with an agonist of miR-21 to experimental mice and a control mouse with an NC-agonist, wherein the NC-agonist is a gene fragment similar in length to the agonist of miR-21, but does not bind to the site, does not act, and measures changes in blood glucose, body weight and lipid metabolism. The specific logic process is as follows:

first, the body weights of WT and miR-21 β KO mice with sizes of 7 weeks and 27 weeks and the blood sugar of the mice are measured, and specific results can be seen in fig. 4a-4d, wherein fig. 4a is a schematic diagram of a body weight control of WT and miR-21 β KO mice with sizes of 7 weeks, fig. 4b is a schematic diagram of a body weight control of WT and miR-21 β KO mice with sizes of 27 weeks, fig. 4c is a schematic diagram of a blood sugar control of WT and miR-21 β KO mice with sizes of 7 weeks, and fig. 4d is a schematic diagram of a blood sugar control of WT and miR-21 β KO mice with sizes of 27 weeks.

Next, the pancreas of WT and miR-21 β KO mice of 7 and 27 weeks size was cryosectioned and subjected to immunofluorescent staining with insulin (insulin) as shown in FIGS. 5 a-5 f, FIG. 5a is a graph showing immunofluorescent staining of WT and miR-21 β KO mice of 7 weeks size, FIG. 5b is a graph showing immunofluorescent staining of WT and miR-21 β KO mice of 27 weeks size, FIG. 5c is a graph showing a comparison of the number of cells of WT and miR-21 β KO mouse β of 7 weeks size, FIG. 5d is a graph showing a comparison of the number of cells of WT and miR-21 KO β of 7 weeks size, FIG. 5e is a comparison of the number of cells of WT and miR-21 KO β of 27 weeks size, FIG. 5f is a graph showing that after knockout of the WT and miR-21 of miR-7 weeks size affects the number of cells of mice of 7 weeks and miR-27 weeks size mice of miR- β and miR- β mice develop no difference of insulin (insulin).

Next, in one aspect, an agonist of miR-21 or NC is injected into an 8-week-old db/db mouse, as shown in FIGS. 6a and 6b, FIG. 6a is a schematic diagram illustrating a detailed process of miR-21 agonist or NC treatment, and FIG. 6b is a schematic diagram illustrating blood glucose level detection at different time points. The results show that agonist treatment of miR-21 can effectively reduce the blood glucose level of type 2 diabetic mice.

On the other hand, 8-week-sized db/db mice were injected with agonist of miR-21 or NC, the mice were sacrificed on day 11, and the detailed procedure of agonist or NC treatment of miR-21 can be seen in FIG. 6 a. Islet cells of mice after sacrifice are taken to detect the expression of mRNA and protein of Glut2, and the results show that the agonist treatment of miR-21 increases the expression of Glut2, and the results are shown in FIGS. 7a and 7b, FIG. 7a is a comparison graph of the agonist of miR-21 and the expression level of Glut2 after NC treatment, and FIG. 7b is a comparison graph of the agonist of miR-21 and the expression level of Glut2 and protein after NC treatment; the post-mortem mice were serum tested for insulin levels and the results are shown in FIG. 7c, which is a comparison of miR-21 agonist and NC-treated insulin levels. The results show that treatment with an agonist of miR-21 can increase insulin production.

In yet another aspect, a detailed procedure for miR-21 agonist or NC treatment of db/db mice of 8 weeks size by injection of miR-21 agonist or NC, mice sacrificed on day 11, see FIG. 6 a. please refer to FIG. 8a, FIG. 8a is a graphical representation of results from measuring body weight at different time points, showing that there is no significant difference in body weight of the miR-21 agonist treated group from the NC group, see FIG. 8b, FIG. 8b is a graphical representation of results from TG, TCHO, HD L-C, L D L-C in the mouse serum after sacrifice of the mice on day 11, wherein TG is triglyceride, TCHO is total cholesterol, HD L-C is high density lipoprotein cholesterol, L D L-C is low density lipoprotein cholesterol, and showing that the above-mentioned indicators of the miR-21 agonist treated group are not significantly different from the NC group.

Taken together, the above-described achievement process shows that blood glucose is significantly reduced in mice treated with miR-21 agonist, while body weight and lipid metabolism are not significantly altered. In addition, the level of insulin in the blood of mice after miR-21 agonist treatment is obviously increased compared with that of an NC group, and the mRNA and protein expression of Glut2 in pancreas is obviously increased compared with that of a control group, which indicates that the miR-21 agonist can generate more insulin by increasing the expression of Glut2, and finally leads to the reduction of blood sugar.

The above description is only for the purpose of illustrating embodiments of the present application and is not intended to limit the scope of the present application, and all modifications of equivalent structures and equivalent processes, which are made by the contents of the specification and the drawings of the present application or are directly or indirectly applied to other related technical fields, are also included in the scope of the present application.

SEQUENCE LISTING

<110> Shenzhen advanced technology research institute of Chinese academy of sciences

<120> a medicine for preventing/treating type 2 diabetes and use thereof

<160>2

<170>PatentIn version 3.5

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<211>22

<212>RNA

<213> Artificial Synthesis

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uagcuuauca gacugauguu ga 22

<210>2

<211>22

<212>RNA

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aucgaauagu cugacuacaa cu 22

Claims

1. The medicine for preventing/treating type 2 diabetes is characterized in that an active component in the medicine takes miR-21 as a target point and the miR-21 is promoted in a targeted manner.

2. The medicament according to claim 1,

the active component of the medicine comprises an agonist of miR-21.

3. The medicament according to claim 1,

the active component of the medicament comprises a mimic of miR-21.

4. The medicament according to claim 1,

the active component of the medicine comprises an analogue of miR-21.

5. The medicament according to any one of claims 1 to 4,

the gene sequence in the active component of the medicine comprises:

5'-UAGCUUAUCAGACUGAUGUUGA-3' as sense strand;

antisense strand 3 '-AUCGAAUAGUCUGACUACAACU-5'.

6. The medicament of claim 1, further comprising:

a pharmaceutically acceptable carrier for said active ingredient.

7. Application of miR-21 agonist in preparation of medicine for preventing/treating type 2 diabetes is provided.

8. The use according to claim 7, wherein the gene sequence of the agonist of miR-21 comprises:

5'-UAGCUUAUCAGACUGAUGUUGA-3' as sense strand;

antisense strand 3 '-AUCGAAUAGUCUGACUACAACU-5'.

9. Application of miR-21 mimics in preparation of medicines for preventing/treating type 2 diabetes.

10. An application of an analog of miR-21 in preparation of a medicament for preventing/treating type 2 diabetes.