Application of Mup3 recombinant protein in treatment of type 2 diabetes mellitus

Abstract

The invention is applicable to the technical field of biology, and provides application of a Mup3 recombinant protein in treatment of type 2 diabetes mellitus, and the amino acid sequence of the Mup3 recombinant protein is shown as SEQ ID NO.1 in a sequence table; the Mup3 recombinant protein provided by the invention is small in side effect, and the mechanism of the Mup3 recombinant protein playing a role is to directly inhibit the gluconeogenesis gene and enhance the insulin sensitivity, so that the hypoglycemic effect is obvious. The compound can play a role in treatment of type 2 diabetes mellitus, and can be further applied to prevention and treatment of other related diseases by deep research on enhancement of an insulin signal channel.

Description

Technical Field

[0001] The invention belongs to the field of biotechnology, and in particular relates to application of Mup3 recombinant protein in treating type 2 diabetes. Background Art

[0002] Diabetes mellitus (T2D) is a chronic disease characterized by hyperglycemia caused by multiple etiologies. It is a metabolic disorder caused by insufficient insulin secretion by pancreatic β cells or reduced insulin sensitivity, which leads to insufficient glucose uptake and utilization by peripheral tissues. It mainly includes carbon metabolism and lipid metabolism disorders. It is a slowly progressive metabolic obesity disease. The prevention and treatment strategy for diabetes mellitus is a comprehensive prevention and treatment measure including "seven carriages" such as diet therapy, reasonable exercise, disease monitoring, drug therapy, education management, psychological counseling, and complication prevention. my country's T2D follows a three-level prevention and treatment strategy. Among them, the first level is to prevent the onset of T2D by controlling the risk factors for the onset of T2D; the second level is early detection, early diagnosis, and early treatment of diabetes; the third level is to delay and reduce the disability rate and mortality rate as well as the disease progression of diabetic patients and improve the quality of life of patients. There are 12 types of glucose-lowering drugs currently on the market for the treatment of type 2 diabetes, including metformin, thiazolidinediones, α-glucosidase inhibitors, sulfonylureas, glinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagonlike peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporterprotein-2 (SGLT-2) inhibitors, amylin analogs, bile acid sequestrants, dopamine receptor agonists and insulin / insulin analogs.

[0003] The main hypoglycemic drugs used in my country include insulin, biguanides, α-glucosidase inhibitors, sulfonylureas, glinides, DPP-4 inhibitors, thiazolidinediones and GLP-1 receptor agonists. Insulin has the strongest hypoglycemic effect among all drugs, and many other hypoglycemic drugs also lower blood sugar by promoting insulin secretion or enhancing the function of insulin. At present, there are mainly two types of insulin drugs: exogenously expressed human insulin and modified insulin analogs, both of which are used by subcutaneous injection. According to the onset time and half-life, insulin is divided into basal insulin, rapid-acting insulin, short-acting insulin and medium- and long-acting insulin. There are also premixed insulin products based on various insulin combinations. Long-term use of insulin has the risk of weight gain. In addition, due to the strong hypoglycemic effect of insulin, improper use of insulin can easily cause hypoglycemia. Therefore, there are many things to pay attention to when using it, such as the type of insulin used, the dosage, the time and frequency of use, etc. In addition, in patients with renal damage, the insulin dosage needs to be appropriately lowered.

[0004] Metformin has been used in clinical practice since the 1950s and is the most widely used first-line drug for type 2 diabetes. However, its exact mechanism of action is still not clear. Metformin is mainly metabolized by the kidneys. Therefore, it is not effective in patients with severe renal insufficiency (estimated glomerular filtration rate eGFR < 30 mL / min / m 2 Metformin may cause some common gastrointestinal side effects, such as nausea and vomiting. In addition, long-term use of metformin may cause vitamin B12 deficiency.

[0005] Sulfonylureas target the pancreas and promote insulin secretion by blocking ATP-dependent potassium channels, thereby lowering blood sugar levels. The main side effect of sulfonylureas is hypoglycemia. In addition, this type of drug can also cause some minor side effects such as headache, dizziness, nausea, allergies, etc., and weight gain is also common. Sulfonylureas are contraindicated in patients with impaired liver and kidney function, and are also contraindicated in pregnant women because they may cause neonatal hypoglycemia. Some drugs such as aspirin, sulfonamides, allopurinol and fibrates may enhance their function when used with sulfonylureas, which can easily cause hypoglycemia, so caution is required when using them. In addition, sulfonylureas may significantly increase the risk of hypoglycemia when used in combination with some other hypoglycemic drugs. The US FDA specifically warns that first-generation sulfonylureas (tolbutamide) have an increased risk of cardiovascular death and should be avoided as much as possible. Glinides are non-sulfonylurea insulin secretagogues. Like sulfonylureas, they can also bind to sulfonylurea receptors in pancreatic cells through the same mechanism of action. However, glinides bind more weakly to sulfonylurea receptors than sulfonylureas and can therefore be considered short-acting insulin secretagogues.

[0006] Similar to biguanides, thiazolidinediones can also promote the action of insulin, and their representative drugs include rosiglitazone and pioglitazone. Thiazolidinediones are agonists of peroxisome proliferator-activated receptors, which can promote glucose absorption in many tissues such as fat cells, muscle cells and liver. Its mechanism of action is to improve insulin resistance and beta cell damage by reducing the accumulation of free fatty acids, reducing the production of inflammatory cytokines, increasing adiponectin levels and protecting cell integrity and function. However, compared with the effects of thiazolidinediones, the side effects they cause may be more serious. When thiazolidinediones are used in combination with insulin, heart failure can occur. In addition, thiazolidinediones can cause edema, heart failure, and lead to the risk of fractures. Rosiglitazone can cause increased low-density lipoprotein cholesterol, while pioglitazone can also cause bladder cancer.

[0007] Both DPP-4 inhibitors and GLP-1 receptor agonists target the incretin secretion system. DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin, linagliptin, and alogliptin. These drugs can be used alone or in combination with metformin, sulfonylureas, and thiazolidinediones. In clinical trials, common side effects of DPP-4 inhibitors include nasopharyngitis, upper respiratory tract infections, and headaches. In addition, they may cause acute pancreatitis and joint pain. When the dose is adjusted down, DPP-4 inhibitors can be used in patients with moderate and severe renal impairment. GLP-1 receptor agonists include lixisenatide, exenatide, and liraglutide. GLP-1 receptor agonists have increased resistance to the enzymatic activity of DPP-4. For newly diagnosed patients with type 2 diabetes who are obese and have abnormal metabolic profiles, the use of GLP-1 receptor agonists can not only lower blood sugar, but also reduce weight and improve metabolic disorders. However, this type of drug should be used with caution or contraindicated in patients with renal impairment. GLP-1 receptor agonists are well tolerated, and common side effects are mainly gastrointestinal reactions, including nausea and vomiting. However, this type of drug may also cause thyroid C-cell tumors.

[0008] α-Glucosidase inhibitors mainly reduce postprandial blood sugar levels by inhibiting the absorption of carbohydrates in the small intestine. They are suitable for patients whose diet mainly consists of starchy foods and whose postprandial blood sugar is elevated. In the 2017 version of the Guidelines for the Prevention and Treatment of Type 2 Diabetes in my country, α-Glucosidase inhibitors are recommended as a first-line alternative to metformin. The main α-Glucosidase inhibitors in my country include acarbose, voglibose, and miglitol. Perhaps due to different dietary structures, α-Glucosidase inhibitors are not officially recommended for use in the United States. The common side effects of α-Glucosidase inhibitors are mainly gastrointestinal discomfort, such as abdominal distension and flatulence.

[0009] The sodium-glucose transporter SGLT distributed in the renal tubules reabsorbs 99% of the filtered glucose during renal filtration. The main subclass of SGLT in the renal tubules is SGLT-2, so SGLT-2 inhibitors can lower blood sugar by increasing the amount of glucose excreted in the urine. The main SGLT-2 inhibitors currently include dapagliflozin, empagliflozin and canagliflozin. Because they do not rely on glucose to function, this type of drug is mainly used when type 2 diabetes progresses to the point where pancreatic beta cells basically lose their function. Because they function through the kidneys, SGLT-2 inhibitors should be used with caution or contraindicated in patients with renal damage. In addition, SGLT-2 inhibitors may also cause a series of side effects. Canagliflozin can cause the risk of fractures and amputations. Although it is rare in patients with type 2 diabetes, all SGLT-2 inhibitors have the risk of causing diabetic ketoacidosis. Other side effects that have been reported more frequently include the risk of causing urogenital infections and hypovolemia and leading to hypotension. In addition, SGLT-2 inhibitors can cause elevated LDL-C and increase the risk of vascular complications.

[0010] Different hypoglycemic drugs have different mechanisms of action and cause different side effects. Therefore, the contraindications and precautions for use are also different. In general, hypoglycemic drugs should be used with extreme caution in patients with type 2 diabetes who are at higher risk of renal damage and cardiovascular disease, and should be used with caution based on the patient's various clinical indicators. In addition, the use of drugs in obese patients and patients with various complications or comorbidities should also comprehensively consider drug toxicity, side effects, and interactions between drugs.

[0011] The pathogenesis of type 2 diabetes is multifaceted, including genetic and environmental factors, and its main characteristics are hyperglycemia and insulin resistance. In normal people, the body's insulin secretion level increases after eating, thereby promoting the uptake of glucose by peripheral tissues such as skeletal muscle and adipose tissue; in type 2 diabetes, insulin resistance increases the synthesis of glucose in the liver while reducing the absorption of glucose by muscle and adipose tissue, causing an increase in blood glucose levels; in addition, pancreatic β-cell dysfunction can also lead to reduced insulin secretion, which cannot effectively maintain the body's blood glucose homeostasis. Recent studies have confirmed that increased glucagon levels are also a significant common feature of type 1 and type 2 diabetes. Under starvation conditions, increased glucagon secretion promotes liver gluconeogenesis and increases blood glucose levels. Clinical studies have also confirmed that the glucagon content in the blood of patients with type 2 diabetes is significantly increased. In animal models, reducing glucagon levels can effectively improve the hyperglycemia symptoms of diabetic mice. In type 2 diabetes, the abnormal increase in liver gluconeogenesis caused by insulin resistance is closely related to hyperglycemia and its diabetic syndrome. Hyperglycemia after starvation is also a significant feature of type 2 diabetes, mainly due to disorders in liver glucose synthesis. Diabetic patients usually have higher gluconeogenesis levels and higher blood sugar levels when they are hungry. Glucose synthesized by liver gluconeogenesis accounts for about 90% of endogenous glucose, so controlling liver glucose synthesis is also a very important goal in the clinical treatment of type 2 diabetes. In summary, it is urgent to find a new solution for treating and / or preventing and / or alleviating and / or improving type 2 diabetes to circumvent the above problems. Summary of the invention

[0012] The purpose of the embodiments of the present invention is to provide an application of a Mup3 recombinant protein in treating type 2 diabetes, aiming to solve the problems raised in the background technology.

[0013] In view of the above problems, the embodiment of the present invention is implemented as follows: a marker for enhancing insulin sensitivity includes a Mup3 recombinant protein; the amino acid sequence of the Mup3 recombinant protein is shown in the sequence table SEQ ID NO.1.

[0014] Another object of the present invention is to provide a use of Mup3 recombinant protein in the preparation of a drug for enhancing insulin sensitivity.

[0015] Another object of the present invention is to provide a use of Mup3 recombinant protein in the preparation of a medicament for treating and / or preventing type 2 diabetes.

[0016] Another object of the present invention is to provide a drug for treating and / or preventing type 2 diabetes, comprising a biologically acceptable carrier and a Mup3 recombinant protein.

[0017] Compared with the prior art, the present invention has the following advantages:

[0018] The Mup3 recombinant protein provided by the present invention has few side effects, and the mechanism of the Mup3 recombinant protein is to directly inhibit gluconeogenesis genes, enhance insulin sensitivity, and have a more significant hypoglycemic effect. In addition to playing a role in the treatment of type 2 diabetes, in-depth research on enhancing the insulin signaling pathway can be further applied to the prevention and treatment of other related diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This figure shows the effect of Mup3 recombinant protein on the expression levels of CCAAT enhancer binding protein α and downstream key enzyme genes involved in gluconeogenesis.

[0020] Figure 2 This is a graph showing the effect of Mup3 recombinant protein on the insulin signaling pathway.

[0021] Figure 3 This is a graph showing the effect of Mup3 recombinant protein on glucose secretion. DETAILED DESCRIPTION

[0022] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0023] Major urinary protein 3 (Mup3) is a member of the Mups family. Mups belongs to the lipid transport protein superfamily, with a molecular weight of about 18-19kDa. Its content in the excreted urine is very high. Like other lipoproteins, Mups can bind to small organic molecules such as pheromones to affect the sexual and social behaviors of animals. Mups proteins themselves can also affect the above behaviors of animals. This family includes 21 members, and there is a high degree of sequence homology between different family members. Mups are highly expressed in the liver, while the expression level in some secretory tissues is low. Studies have shown that the expression of Mups in mouse liver can be regulated by zinc fingers and homeoboxes 2 (Zhx2), and Zhx2 can promote the expression of related Mups family members. Mups are very sensitive in the mouse vomeronasal bone and can promote the regeneration, survival and proliferation of neurons. In addition to its chemical information exchange function, Mups family members also participate in the regulation of metabolic functions of the body; for example, Mup1 participates in the regulation of liver glucose and lipid metabolism in mice, and improves glucose tolerance and insulin sensitivity in diabetic mice by increasing the body's energy consumption. The expression level of Mup1 in the liver of obese mice and type 2 diabetic mice is significantly reduced. Upregulating the expression of Mup1 in the liver can inhibit the expression of key genes for gluconeogenesis and fat synthesis. In addition, the expression levels of multiple Mups family members such as Mup5 and Mup3 in the liver of normal C57BL / 6J mice are significantly reduced after dietary restriction, and their expression levels return to normal after normal feeding, indicating that the expression of Mups is regulated by the body's nutritional status. In addition, studies have confirmed that resveratrol, a drug that increases insulin sensitivity, can induce the expression of Mup1 and Mup3, which also suggests that Mup3 may be related to the body's insulin sensitivity.

[0024] Specifically, in one embodiment of the present invention, a marker for enhancing insulin sensitivity is provided, which includes Mup3 recombinant protein; the amino acid sequence of the Mup3 recombinant protein is shown in the sequence table SEQID NO.1, specifically: EESSSMERNFNVEQISGYWFSIAEASYEREKIEEHGS MRAFVENITVLENSLVFKFHLIVNEECTEMTAIGEQTEKAGIYYMNYDGFNTF SILKTDYDNYIMIHLINKKDGKTFQLMELYGREPDLSLDIKEKFAKLCEEHGIIRENIDLTNVNRCLEAREHHHHHH*.

[0025] In another embodiment of the present invention, there is provided a use of a Mup3 recombinant protein in the preparation of a drug for enhancing insulin sensitivity.

[0026] In another embodiment of the present invention, there is provided a use of a Mup3 recombinant protein in the preparation of a medicament for treating and / or preventing type 2 diabetes.

[0027] In another embodiment of the present invention, a drug for treating and / or preventing type 2 diabetes is provided, comprising a biologically acceptable carrier and a Mup3 recombinant protein.

[0028] The experimental methods in the following examples without specifying specific experimental conditions are usually carried out according to conventional experimental conditions or the experimental conditions recommended by the manufacturer. Unless otherwise specified, the reagents, raw materials and equipment used in the present invention can be obtained from commercial sources.

[0029] Example 1: This example provides a method for preparing a Mup3 recombinant protein, which is synthesized by Shanghai Jinan Technology Co., Ltd. and may specifically include the following steps:

[0030] S1. Construction of plasmid: Using plasmid 6His-Mup3-pET-28a(+) as a template, design specific primers containing Nco I and Hind III restriction sites, and amplify the human Mup3 gene sequence by PCR. Use Nco I and Hind III to simultaneously digest the amplified product and the pRSFDuet vector, recover them separately, connect them with T4 DNA ligase, and transform the ligated product into E. coli DH5α competent cells. After obtaining competent cells, plate and pick single clones, and extract plasmids from the bacteria after mass culture.

[0031] S2. The plasmid extracted above was transfected into 100 mL Expi293 cells according to the requirements of the jetPRIME transfection kit. The transfected 293 cells were collected, and all proteins were further purified by one-step Ni column affinity to obtain Mup3 recombinant protein.

[0032] Example 2: This example provides a method for isolating primary liver cells, which specifically includes the following steps:

[0033] S1. Preparation of each required solution is as follows:

[0034] Solution C: potassium chloride (480 mM);

[0035] Magnesium sulfate MgSO4 (120 mM), potassium dihydrogen phosphate KH2PO4 (120 mM);

[0036] CaCl2 solution: anhydrous calcium chloride (CaCl2) (1M), calcium chloride dihydrate (CaCl2:2H2O) (1M);

[0037] Ethylene glycol ether diamine tetraacetic acid (EGTA) solution: weigh 190.175 mg of EGTA powder, add a small amount of pure water to dissolve the powder, if it is not completely dissolved, add an appropriate amount of sodium hydroxide (NaOH) solution to completely dissolve the EGTA, adjust the pH to neutral with hydrochloric acid (HCl) solution, and finally make up to 10 mL;

[0038] Krebs solution: sodium chloride (NaCl) (3.5 g), sodium bicarbonate (NaHCO3) (1.0 g), glucose (1.8 g), 1 mol / L HEPES (pH = 7.45) 2.5 mL, solution C 5 mL, dilute to 500 mL. All the above solutions are neutral solutions and are stored at 4°C.

[0039] Perfusion fluid I: add 80μL EGTA solution to 40mL Krebs solution; perfusion fluid II: add 61.74μL CaCl2 solution and 0.027g collagenase II to 45mL Krebs solution. Perfusion fluids I and II should be prepared and used immediately. After preparation, put them in a 37℃ water bath to preheat. Inhale 40mL perfusion fluid I with a 50mL syringe in advance and connect it to a No. 4.5 disposable intravenous infusion scalp needle, remove bubbles and set aside.

[0040] S2. Anesthetize mice: Anesthetize mice with 1% sodium pentobarbital (80 mg / kg) injected intraperitoneally.

[0041] S3. Perfusion digestion of the liver: Wipe the anesthetized mouse completely with 75% alcohol, with the abdomen facing up and the limbs fixed. First, cut the skin and stretch it completely, cut the fascia to open the abdominal cavity, expose the liver and separate the inferior vena cava and portal vein. Insert the needle close to the lower end of the inferior vena cava, with a depth of about 0.5 cm, and hold the needle with both hands. Another person begins to push the syringe slowly, and after the liver is filled and fully expanded, cut the portal vein. Push slowly for the first 3 minutes to prevent blood vessels from rupturing due to excessive speed, and then push at a constant speed to allow the blood in the liver to flow out completely. After the liver turns khaki and no blood flows out of the portal vein, connect the perfusion fluid II and push it in slowly and at a constant speed. If cracks or blisters appear in the liver, stop perfusion.

[0042] S4. Remove the liver with elbow forceps and transfer it to a 6 cm culture dish. Cut off the gallbladder in PBS, wash off the blood clots on the surface, transfer to perfusion fluid II, cut the liver lobes, and gently swing the liver lobes to release the hepatocytes. Place a 70 μm plastic filter in the mouth of a 50 mL centrifuge tube in advance, suck the cell suspension into the filter, and add 10 mL of complete culture medium. Centrifuge at 4°C, 500 rpm for 3 minutes, discard the supernatant and resuspend with basal culture medium, repeat 3 times, and centrifuge at 700 rpm for the last time for 5 minutes. Discard the supernatant in the clean bench and resuspend the hepatocytes with pre-cooled 15 mL of complete culture medium. Trypan blue staining was used to observe cell survival rate. If the survival rate was higher than 90%, the cells were plated.

[0043] S5. Plate laying: Gently shake the resuspended hepatocytes continuously, add 200 μL of resuspended hepatocytes to 1.5 mL of complete culture medium in each well of the 6-well plate. Shake the well plate in a "cross" shape and place it in the incubator for culture. After 4-5 hours, change the medium and proceed to the next step of the experiment.

[0044] Example 3: The effect of Mup3 recombinant protein on the expression level of CCAAT enhancer binding protein α (C / EBPα) and downstream key enzyme genes involved in gluconeogenesis was verified in primary mouse liver cells by treating Mup3 recombinant protein, as follows:

[0045] The primary liver cells isolated in Example 2 were replaced with serum-free medium and Mup3 recombinant protein (0.1 mM) was added and cultured for 1 h as the Mup3 experimental group. An equal volume of phosphate buffered saline (PBS) was added to the control group (NC). Both groups were treated with 10 μM adenylate cyclase activator (Forskolin, Fsk) and 1 μM dexamethasone (Dexamethasone, Dex). After further culture for 6 hours, total cell RNA and protein were collected, and the mRNA and protein expression levels of C / EBPα and downstream target genes such as phosphoenolpyruvate carboxykinase (phosphoenolpyruvate carboxykinase, PEPCK) and glucose-6-phosphatase (glucose-6-phosphatase, G6PC) were detected by q-PCR and Western-blot methods to analyze whether up-regulating Mup3 inhibited the expression of key gluconeogenesis genes. The results are shown in Figure 2. Figure 1 As shown in A and B.

[0046] The results showed that treatment of mouse liver primary cells with recombinant Mup3 protein significantly reduced the expression of gluconeogenesis-related genes.

[0047] Example 4: The effect of Mup3 recombinant protein on the insulin signaling pathway was verified in primary mouse liver cells by treating Mup3 recombinant protein, as follows:

[0048] The primary liver cells isolated in Example 2 were replaced with serum-free culture medium and Mup3 recombinant protein (0.1 mM) was added and cultured for 1 h as the Mup3 experimental group. The control group (NC) was added with an equal volume of phosphate buffered saline (PBS). Both groups were treated with insulin (100 mM, insulin, Ins) for 5 min, and cell proteins were collected to detect the expression levels of proteins related to the insulin signaling pathway. The effect of up-regulating Mup3 on the insulin signaling pathway was analyzed. The results are shown in FIG. Figure 2 shown.

[0049] The results showed that after mouse liver primary cells were treated with Mup3 recombinant protein, the phosphorylation levels of AKT, GSK-3β and FOXO1 were significantly increased, indicating increased insulin sensitivity.

[0050] Example 5: Conducting a glucose output test on mouse liver primary cells, as follows:

[0051] The primary hepatocytes isolated from Example 2 were cultured evenly in a 6-well plate containing RPMI-1640 complete medium. After about 12-16 hours, the cells were replaced with fresh RPMI-1640 complete medium, and Mup3 recombinant protein (0.1mM) was added for culture for 1 hour as the Mup3 experimental group. The control group (NC) was added with an equal volume of phosphate buffered saline (PBS), and both groups of cells were rinsed three times with cooled PBS. Afterwards, the cells were cultured with a special DMEM medium without phenol red and glucose, and the medium contained 20mM sodium lactate, 2mM sodium pyruvate, 1μM DEX and 10μM adenylate cyclase activator (Forskolin, FSK). After 3 hours, about 0.5mL of the culture medium was collected to detect the concentration of glucose according to the glucose assay Kit (Applygen Technologies Inc). At the same time, the cells in each well were collected for lysis and the cell protein concentration in each well was detected. The concentration of glucose in each well was corrected by the total protein concentration in each well to obtain the experimental results, as shown in the following figure. Figure 3 shown.

[0052] The results showed that Mup3 recombinant protein could reduce the secretion of glucose in mouse liver primary cells.

[0053] In summary, the Mup3 recombinant protein provided in the embodiments of the present invention has few side effects, and the mechanism of the Mup3 recombinant protein is to directly inhibit gluconeogenesis genes, enhance insulin sensitivity, and have a more significant hypoglycemic effect.

[0054] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A marker for enhancing insulin sensitivity, characterized in that: It comprises Mup3 recombinant protein; the amino acid sequence of the Mup3 recombinant protein is shown in the sequence table SEQ ID NO.

1.

2. Use of Mup3 recombinant protein in the preparation of a drug for enhancing insulin sensitivity, characterized in that: The amino acid sequence of the Mup3 recombinant protein is shown in the sequence listing SEQ ID NO.

1.

3. Use of Mup3 recombinant protein in the preparation of a drug for treating and / or preventing type 2 diabetes, characterized in that: The amino acid sequence of the Mup3 recombinant protein is shown in the sequence listing SEQ ID NO.

1.

4. A drug for treating and / or preventing type 2 diabetes, comprising a biologically acceptable carrier, characterized in that: It also includes Mup3 recombinant protein; the amino acid sequence of the Mup3 recombinant protein is shown in the sequence table SEQ ID NO.1.

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