CN117205322A - Application of FER1L6 gene in diabetes prevention and treatment - Google Patents

Abstract

The application belongs to the technical fields of biological medicine and molecular biology, and particularly relates to application of FER1L6 gene in diabetes prevention and treatment. When the preparation is applied, the expression level of GLUT4 is increased by inhibiting the expression of FER1L6, so that the preparation is used for improving the related physiological metabolism of organisms suffering from diabetes; the physiological metabolism includes: glucose uptake, lipid metabolism, oxidative stress injury. Experimental results show that FER1L6 is highly expressed in type 2 diabetic mice and insulin resistant HepG2 cells; after the expression of FER1L6 is reduced, the expression level of GLUT4 can be obviously increased, and finally, the lipid metabolism and oxidative stress injury of diabetic mice can be improved, and the absorption of cells to glucose can be improved. From this it can be assumed that: FER1L6 is a better regulation target when preventing and treating type 2 diabetes based on GLUT4 path. Based on the target spot, a new technical idea can be provided for prevention and control of type 2 diabetes.

Description

Application of FER1L6 gene in diabetes prevention and treatment

Technical Field

The application belongs to the technical fields of biological medicine and molecular biology, and particularly relates to application of FER1L6 gene in diabetes prevention and treatment.

Background

Diabetes is a metabolic disease characterized by hyperglycemia, and clinically, it is classified into type 1 diabetes and type 2 diabetes (T2 DM) according to clinical symptoms, age, and other factors. Among them, type 2 diabetes (T2 DM) is a major clinical feature of chronic hyperglycemia.

The direct cause of diabetes is mainly caused by insufficient insulin secretion or reduced peripheral insulin sensitivity. The number of ill people is great, and has become one of the important issues of global public health concern. For this disease, diet, exercise and drug therapy are combined as a common strategy for treating diabetes. Clinically, the drug therapy mainly comprises oral hypoglycemic agents and insulin injections. However, hypoglycemia is also a common side effect of these drugs, and in addition, long-term insulin injection is also possible to enhance insulin resistance, so early prevention is still a main control strategy for diabetes, and development of new therapeutic targets is also a main technical effort direction in diabetes control.

Insulin resistance is a common condition in the control of T2DM, for which enhancing insulin sensitivity is a common and effective control strategy. Related metabolic pathway studies indicate that glucose uptake following insulin stimulation requires mediation by glucose transporter 4 (GLUT 4). And GLUT4 has an ultra-long half-life (more than 24 hours) and a slow recovery rate, so that the protein has better stability and targeting in the insulin stimulation reaction process. Studies on T2DM patients show that one of the typical features of T2DM patients is an impaired GLUT4 membrane translocation mechanism and a reduced expression level. Related mouse experimental researches show that GLUT4 knockout mice show symptoms of insulin resistance and glucose intolerance and have a diabetes phenotype; whereas GLUT4 overexpressed mice showed improved insulin action and reduced blood glucose levels in both fasted and postprandial states. Based on the research results, the intensive research on GLUT4 expression related proteins can provide more technical ideas for the prevention and treatment of T2DM.

Disclosure of Invention

Based on the summary of related existing researches of the Ferlin protein family, by taking an insulin resistance cell model as an experimental material and combining the importance of GLUT4 in glucose transport, the inventor considers FER1L6 as an important target point in the prevention and treatment of type 2 diabetes, and based on the result, a good technical foundation can be laid for further perfecting related insulin metabolism regulation mechanisms and developing novel diabetes medicines.

The technical scheme adopted by the application is detailed as follows.

Use of FER1L6 gene in the prevention and treatment of diabetes mellitus, which is type 2 diabetes mellitus (T2 DM); FER1L6 is highly expressed in type 2 diabetes organisms and insulin resistant HepG2 cells, and inhibition of FER1L6 expression can significantly increase GLUT4 expression level, thereby improving lipid metabolism and oxidative stress injury of the diabetes organisms;

such lipid metabolism-related genes include, but are not limited to, triglycerides (TG) and Total Cholesterol (TC);

the oxidative stress indicators include, but are not limited to, superoxide dismutase (SOD) and Malondialdehyde (MDA);

the specific mode of inhibiting the expression of FER1L6 is as follows: RNA interfering molecules or antisense oligonucleotides, small molecule inhibitors, sirnas are designed against FER1L6 to inhibit transcription and expression of FER1L6 by means of lentiviral infection or gene knockout, or specific antibodies (i.e., e.g., anti-FER 1L6 antibodies) are designed against FER1L6 itself or molecules upstream and downstream thereof.

Studies have shown that the Ferlin protein family includes at least six members: : dysferlin (FER 1L 1), otoferlin (FER 1L 2), myoferlin (FER 1L 3), FER1L4, FER1L5, and FER1L6 according to the present application. Common features of these proteins in terms of structure include: multiple Ca' s ²⁺ Binding to the C2 domain, the FerA domain and the transmembrane domain membrane anchored by its single C-terminus, this family of proteins is considered to be in Ca ²⁺ Triggered membrane fusion and vesicle transport play an important role, so that the genes of this family have close correlation with the occurrence and development of various diseases. The results of related studies on the association of this family of proteins with insulin indicate that: FER1L3 is capable of mediating endocytic cycle and is involved in the transport of insulin-like growth factor receptors; fer1L5 protein directlyThe endocytic circulating proteins EHD1 and EHD2 bind, whereas EHD2 may be involved in insulin-induced transport of GLUT4 to the cell membrane in rat adipocytes. However, only a part of the functional studies on FER1L6 have been reported on the muscle formation during the development of zebra fish, and no study has been reported on whether FER1L6 protein is involved in the metabolism of sugar and even in the prevention and treatment of T2DM.

In combination with related research results related to the Ferlin protein family in the prior art, the inventor performs related experimental research on the application prospect of FER1L6 in glucose metabolism and T2DM. Preliminary experimental results show that FER1L6 is highly expressed in type 2 diabetic mice and insulin resistant HepG2 cells (according to which it can be primarily determined that elevated levels of FER1L6 lead to or accompany the development of diabetes); further, the in-vivo experimental result of knocking down the FER1L6 shows that after the expression of the FER1L6 is reduced, the expression level of GLUT4 can be obviously increased, the lipid metabolism and oxidative stress injury of a diabetic mouse are finally improved, and meanwhile, the related cell experiment also proves that the absorption of cells to glucose can be improved by reducing the expression of the FER1L6.

Based on the relevant experimental evidence of the present application, the inventors considered: FER1L6 is a better regulation target when preventing and treating type 2 diabetes based on GLUT4 path. Based on the target spot, a new technical idea can be provided for prevention and control of type 2 diabetes mellitus, and meanwhile, a better reference and reference are provided for development of other types of medicines.

Drawings

FIG. 1 is a graph showing the results of a correlation test during the construction of an insulin resistance cell model; wherein:

a is the result of glucose uptake difference after HepG2 cells are treated by different concentrations of GlcN;

b is the verification result of the insulin resistance cell model by adding insulin treatment;

c is a volcanic map of the differential gene after transcriptomic analysis of GlcN-vs-Control cells;

d is further detection of the condition of the expression quantity of the 5 genes with obvious difference in expression by qRT-PCR; and (3) injection: comparison with blank groupP<0.05，**P<0.01，***P<0.001; with LPS groupIn comparison with the comparison result of the comparison, ^# P<0.05， ^## P<0.01， ^### P<0.001；

FIG. 2 shows the results of a correlation test after gene silencing FER1L 6; wherein:

a is the detection result of FER1L6 expression after gene silencing;

b is the detection result of glucose absorption after gene silencing;

c is the detection result of the gene expression condition of GLUT4 after gene silencing;

d is the detection result of GLUT4 protein expression after gene silencing; and (3) injection: comparison with blank groupP<0.05，**P<0.01，***P<0.001; in comparison with the set of models, ^# P<0.05， ^## P<0.01， ^### P<0.001；

FIG. 3 shows the results of animal experiments after knocking down the liver FER1L6 of the mice; wherein:

a is the expression quantity of FER1L6 and GLUT4 detected by Western blot technology

B is the quantitative detection result of the FER1L6 protein;

c is the quantitative detection result of GLUT4 protein;

d is the HE and oil red O staining result of the mouse liver;

e is the detection result of the level of triglyceride and total cholesterol in the serum of the mice;

f is the level detection result of superoxide dismutase and malondialdehyde in the liver of the mouse; and (3) injection: comparison with blank groupP<0.05，**P<0.01，***P<0.001; in comparison with the set of models, ^# P<0.05， ^## P<0.01， ^### P<0.001；

in the figure: "HFD" is a high fat diet feeding group; AAV8-shCtrl is a gene silencing control group; alloxan is a model set; AAV8-shFeril6 is a gene silencing group.

Detailed Description

The application is further illustrated by the following examples. Before describing the specific embodiments, the following description will briefly explain some experimental contexts in the following embodiments.

Biological material:

HepG2 cells (liver cancer cells) purchased from the China academy of sciences typical culture Collection Committee cell bank; the culture conditions are as follows: in DMEM medium containing 10% fetal calf serum and 1% penicillin and 5% CO at 37deg.C ₂ Culturing in an incubator;

the related primer synthesis and sequencing work is completed by Huada gene technology limited company;

c57BL/6 male mice (4 weeks old) were purchased from Liaoning Long Biotechnology Co., ltd (SCXK 2020-0001).

Example 1

In view of the important technical significance of the diabetes prevention and treatment work, the inventor establishes a certain technical foundation for the diabetes prevention and treatment work or the development of novel medicines by constructing a cell model of insulin resistance and screening and excavating related key regulatory genes. The relevant test cases are briefly described below.

Construction of insulin resistance cell model

HepG2 cells were grown at 4X 10 ⁴ The density of the cells/hole is inoculated in a 96-well plate, after the cells are attached to the wall after about 24-h are cultured, the complete culture medium is replaced by a serum-free high-sugar DMEM culture medium, and the culture is continued for 12 h (so as to starve the cells);

subsequently, the cells were treated separately in different groups:

blank control group: discarding the old culture medium, and adding a new DMEM culture medium;

test group (insulin resistance model group): the medium was replaced with DMEM medium containing GlcN (glucosamine) at different concentrations, which were set to: 1. 4, 8, 12, 16 and 20 mmol/L;

after the relevant treatment group was placed in an incubator and the culture treatment was continued for 24 h, the glucose content in the cell supernatant was detected by the GOD-POD method, and the amount of glucose taken up by the cells during this period was calculated.

The experimental results showed (the results are shown in fig. 1A of fig. 1): when the HepG2 cells are treated by GlcN with different concentrations, the consumption of glucose by the cells can be obviously inhibitedP<0.001 And such inhibition is exhibitedDose dependence.

Based on the GlcN treatment described above, the cells of the different test groups were replaced with DMEM medium supplemented with insulin (see prior art documents and considering factors such as convenience of operation, the amount of insulin was set to 3 μm), and after further culturing 24. 24 h, the amount of glucose taken up by the cells was detected and calculated (to evaluate whether the HepG2 cell-based insulin resistance model was successful).

The results showed (fig. 1B): compared with a blank control group, the insulin can obviously promote the glucose uptake of HepG2 cells after being addedP<0.001 A) is provided; while GlcN treated groups 8, 12, 16 and mM still failed to significantly promote glucose uptake by cells after insulin addition compared to the control group with insulin addition, indicating that cells developed insulin resistance after GlcN treatment, even though insulin addition still failed to increase glucose uptake utilization by cells. Based on this result, subsequent experiments selected a method of GlcN treatment 24 h using 8 mM to induce insulin resistance in HepG2 cells.

(II) further sequencing analysis of the constructed insulin resistance model

To explore novel therapeutic targets for the treatment of diabetes, transcriptomic mRNA quantification was further performed on the aforementioned HepG2 and IR-HepG2 cells (insulin resistant cells). Based on the measurement results, differentially expressed genes were screened using corrected Q <0.001 as a standard. The results are shown in FIG. 1C.

The analysis results show that: in the GlcN-vs-Control differential results, 68 up-regulated differentially expressed genes and 199 down-regulated differentially expressed genes were identified, which also means that these differentially expressed genes may be potential target genes involved in insulin resistance of HepG2 cells (in the case of FER1L6 gene, FER1L6 is highly expressed in insulin resistant HepG2 cells, differential ranking 3, which suggests that elevated levels of FER1L6 may lead to or accompany the development of diabetes).

To further narrow the target gene range, the inventors further selected to significantly up-regulate the first 5 genes, and used qRT-PCR technology to modulate these 5 genes inThe difference between the expression level of insulin resistance and that of the control cells was detected. The results showed (as shown in fig. 1D): FER1L6, CYP3A7-CYP3A5IP, KNG1, HPX and UGT2B15 are all obviously up-regulated in insulin resistance cell model groupP<0.001 And the difference multiple of FER1L6 is highest (about 30 times), for which reason the inventors selected FER1L6 as the subject of further intensive studies.

Example 2

Based on the determination of FER1L6 gene as a study object in example 1 and on the preliminary determination that high expression of FER1L6 has a direct effect on glucose uptake, the inventors further utilized siRNA treatment technology in combination with the prior art for FER1L6 gene study, to reduce the expression level of FER1L6 in IR-HepG2 cells, to further verify the function of the gene. The relevant test procedure is outlined below.

(one) siRNA primer construction

Based on siRNA technology, aiming at FER1L 6-homo1680 target, related primer sequences are designed as follows:

forward direction: 5'-CCGGAAGAUUGGAGAUAAATT-3' the number of the individual pieces of the plastic,

reversing: 5'-UUUAUCUCCAAUCUUCCGGTT-3';

as a control (Negative control), the relevant primer sequences were designed as follows:

forward direction: 5'-UUCUCCGAACGUGUCACGUTT-3' the number of the individual pieces of the plastic,

reversing: 5'-ACGUGACACGUUCGGAGAATT-3';

(II) siRNA transfection

Lipo2000 is used as a transfection reagent, and siRNA primers (primers provided by Hua big genes are in a freeze-dried powder form and can be directly dissolved for application) are introduced into IR-HepG2 cells. In specific operation, reference is made to transfection reagent instructions, or to the following:

IR-HepG2 cells were prepared in advance according to 1X 10 ⁵ Density of individuals/wells was inoculated in 24 well plates for 24 h in preparation for transfection;

during transfection, 50 mu L of serum-free and double-antibody-free MEM culture medium and siRNA (for discussing proper siRNA dosage, the siRNA concentration is 20 mu moL/L, and the dosage is 1, 1.5 and 2 mu L respectively) are added into an EP tube, and the mixture is incubated for 5 min;

meanwhile, another EP tube was taken, 50. Mu.L of serum-free and double-antibody-free MEM medium and 1. Mu.L of Lipo2000 were added, and incubated for 5 min;

mixing the two EP tube solutions, and incubating for 20 min to promote the formation of siRNA-cationic liposome complex;

subsequently, the culture medium in HepG2 cells on the 24-well plate cultured in advance was discarded, 400. Mu.L of serum-free double-antibody-free culture medium was added to each well, and 100. Mu.L of the siRNA-cationic liposome complex was gently mixed;

after that, the culture medium was discarded after further incubation in an incubator for 6 h (for transfection), 500. Mu.L of a new serum-free double antibody-free medium was added to each well, and the culture was continued.

Finally, the change of the sugar value in the cell supernatant is detected when 24, 48 and 72 and h are respectively cultivated, the treatment group cells with the sugar value remarkably changed are collected, the genome (total RNA) is further extracted and reversely transcribed into cDNA, and the corresponding mRNA expression level is detected by using qRT-PCR technology (taking beta-actin as an internal reference).

In qRT-PCR detection, the relevant primer sequence reference was designed as follows:

for the beta-actin gene, the primers were designed as follows:

f primer: 5'-GGCTGTATTCCCCTCCATCG-3' the number of the individual pieces of the plastic,

r primer: 5'-CCAGTTGGTAACAATGCCATGT-3';

for FER1L6 gene, the primer design is:

f primer: 5'-CCAGAGGAGTCACCAAGAAGA-3' the number of the individual pieces of the plastic,

r primer: 5'-GGTGAGGACCAATCCCTTCTC-3';

for GLUT4 gene, primers were designed to:

f primer: 5'-GTGACTGGAACACTGGTCCTA-3' the number of the individual pieces of the plastic,

r primer: 5'-CCAGCCACGTTGCATTGTAG-3';

the 20 μl amplification system reference design is as follows:

2 x SYBR Green qPCR Master Mix (Low ROX)，5 μL；

f primer, 0.8. Mu.L (10. Mu.M);

r primer, 0.8. Mu.L (10. Mu.M);

template cDNA, 10. Mu.L;

Nuclear-Free Water, add to 20. Mu.L;

the reaction procedure is referenced: pre-denaturation, 95 ℃ for 30s; denaturation at 95℃for 15s, denaturation at 60℃for 30s, and extension for 40 cycles; finally, obtaining a dissolution curve and calculating the expression quantity.

In the experimental process, the design is carried out simultaneously: negative control (siRNA Negative control), negative control+glcn treatment control group (8 mM).

Experimental results show that under different siRNA treatment conditions (the using amounts of siRNA are 40, 60 and 80 pmol respectively), the expression of mRNA after FER1L6 gene silencing is obviously reducedP<0.01 A) is provided; however, further glucose uptake assay results showed that there was some difference in glucose uptake under different siRNA treatment conditions, and only under specific siRNA treatment conditions (60 pmol siRNA) the glucose value was significantly reduced (FIG. 2B,P<0.05 In other words, in this amount, the effect of suppressing the expression of FER1L6 is most remarkable.

Further, after the expression of GLUT4 gene and protein after FER1L6 gene silencing (the amount of siRNA used was 60 pmol treatment group) was detected by qRT-PCR and Western Blot technique, the results showed (fig. 2C, fig. 2D): the gene expression quantity of the GLUT4 in the gene silencing group and the GLUT4 protein content are obviously increasedP<0.001）。

These results all indicate that upon knocking down the FER1L6 gene, a significant increase in GLUT4 expression is promoted, thereby improving glucose uptake (or glucose homeostasis) by IR-HepG2 cells.

Example 3

Based on the verification results of the foregoing examples, the inventors further conducted related animal experiments by constructing a mouse model for targeted knocking down of FER1L6 in the liver, and the related experimental conditions were outlined below.

The experimental process comprises the following steps:

after one week of adaptive feeding of C57BL/6 male mice, the experiments were grouped:

normal group: 8. mice were given normal diet and drinking water;

experimental group: taking 16 mice, feeding with high-fat diet for four weeks, administering to the mice intraperitoneally tetraoxypyrimidine (Alloxan, 50 mg/kg), once every two days, three consecutive injections to construct a T2DM mouse model,

after one week, the mice were tested for continuous fasting blood glucose levels of greater than 11.1 mmol/L, and for polydipsia, polyphagia, polyuria, and physical deterioration, the diabetic model was considered successful (one of the major differences between type 1 diabetes and type 2 diabetes is generally considered to be loss of insulin secretion ability, and type 2 diabetes is characterized by insulin resistance, so the model of type 2 diabetes was constructed in this example).

Randomly selecting 8 mice in a diabetes model, and performing tail vein injection on AAV8-GP-1-SJNC (control virus) as a control;

8 additional AAV8-GP-1-FER1L6 virions were injected as FER1L6 knock-down test group;

after the injection was completed, the high-fat diet was continued to be fed for 2 months.

It should be noted that AAV8-GP-1-FER1L6 viral plasmid (targeting target sequence is shown as SEQ ID No.1, concretely: CCGGAAGATTGGAGATAAA) was constructed by Ji Ma company (control viral plasmid is also provided by this company), and before application, the viral plasmid was packaged together with shuttle plasmid and packaging plasmid to infect GP-1 cells and then prepared into viral particles.

Detecting items and results

(1) HE and oil red O staining of mouse livers

After the end of feeding, dissected, and taken mouse liver samples for HE staining analysis and oil red O staining analysis. The specific operation procedure is referred to as follows.

HE staining analysis: the mouse liver sample is fixed with 4% paraformaldehyde for 24 h, dehydrated and waxed, then the waxed tissue is embedded in an embedding machine and then sliced (paraffin slice with the thickness of 4 mu m), hematoxylin and eosin are used for dying the slice, then the slice is dehydrated and sealed, and image acquisition and analysis are carried out under a microscope.

When liver samples were stained for oil red O: liver tissue was first fixed with 4% paraformaldehyde for 24 h ex vivo, frozen sections (thickness 4 μm) overnight at-80 ℃ after oct embedding, washed with PBS and stained with oil red O using an oil red O staining kit (C0157S, bi yun day) with reference to the instructions.

The experimental results are shown in fig. 3 (fig. 3D), and the analysis can be seen: HE staining results show that compared with other mice in treatment groups, the AAV8-shFer1l6 group with gene silencing has orderly hepatocyte arrangement, and obviously reduced lipid deposition, cell edema and inflammatory cell infiltration; oil red O staining results show that compared with other treatment groups, the lipid droplets of the AAV8-shFer1l6 group mice with the gene silencing function are obviously reduced, and the volume of the lipid droplets is relatively smaller.

(2) FER1L6 and GLUT4 expression

The expression of FER1L6 and GLUT4 proteins was detected and analyzed by Western blot. The specific operation process is referred as follows:

after the crushed liver tissue is cracked by using a lysate (RIPA cell lysate: protease phosphatase inhibitor: PMSF protease inhibitor=100:1:1), the cracked product is centrifuged for 10 min at 4 ℃ and 12000 r/min, and a supernatant is left;

measuring the protein concentration in the supernatant by using a BCA protein quantification kit, adding a5 Xprotein loading buffer solution to dilute the buffer solution to 1X, carrying out high-temperature denaturation at 100 ℃, and sampling (protein sample) to carry out 10% SDS-polypropylene gel electrophoresis separation;

after that, the proteins after electrophoresis gel separation were transferred to a polyvinylidene fluoride membrane (PVDF membrane), and 2 h was blocked with 5% skimmed milk powder;

primary antibodies (FER 1L6, GLUT4 and β -actin) were diluted at a ratio of 1000:1 with TBST (TBS: tween 20=200:1) and used as primary antibody solutions, hybridized with PVDF membranes and incubated overnight at 4 ℃ in a refrigerator;

after incubation, the membrane was washed 5 times (5 min each) with TBST;

then diluting horseradish peroxidase-labeled secondary antibody with TBST according to a ratio of 5000:1 to serve as secondary antibody solution, performing secondary antibody hybridization with the PVDF membrane after TBST membrane washing, and incubating at room temperature for 2 h; after incubation, the membrane was washed 5 times (5 min each) with TBST;

finally, FER1L6, GLUT4 and beta-actin proteins were visualized using ECL luminophor.

The experimental results are shown in fig. 3 (fig. 3C), and the analysis can be seen: after the Fer1l6 gene in the liver of the mouse is knocked down, the Fer1l6 protein content is obviously reduced, but the GLUT4 protein content is obviously increased.

(3) mRNA expression of FER1L6 and GLUT4

The mRNA expression of FER1L6 and GLUT4 was detected by real-time fluorescent quantitative PCR, and the following specific procedures were referred to:

firstly, extracting total RNA of a liver sample by using a Trizol Reagent, and further performing reverse transcription on the RNA into cDNA by using a PrimeScriptTMRT Reagent kit with gDNA Eraser kit;

then, taking the cDNA as a template, and referring to a SYBR (glass-ceramic) Pro Taq HS premixed qPCR kit to perform PCR reaction;

in the reaction process, beta-actin is taken as an internal reference; reference is made to the foregoing for a relevant reaction system;

the reaction conditions are as follows: pre-denaturation at 95 ℃ for 3 min;95 ℃, 5s,60 ℃ and 30s,40 cycles; based on the cyclic threshold (Ct value), the relative expression level of the gene was calculated by the delta method.

The results are shown in FIG. 3 (FIGS. 3A, 3B and 3C). Analysis can be seen: the expression level of the Fer1l6 protein in the liver of the mice is obviously reduced (P < 0.001), and the gene expression level of GLUT4 is obviously increased (P < 0.05).

Further results of the determination of the levels of triglycerides and total cholesterol in the serum of mice from the different treatment groups showed that: upon knock-down of Fer1l6, the levels of triglycerides and total cholesterol in the serum of diabetic mice were significantly reduced (fig. 3E), as well as the levels of superoxide dismutase and malondialdehyde in the liver (fig. 3F). This result shows that by inhibiting the Fer1l6 gene, the diabetic phenotype such as lipid metabolism and oxidative stress injury of diabetic mice can be improved.

Claims (6)

1. Use of FER1L6 gene for preventing and treating diabetes, wherein expression level of GLUT4 is increased by inhibiting expression of FER1L6, and further used for improving physiological metabolism related to organisms suffering from diabetes;

   the physiological metabolism includes: glucose uptake, lipid metabolism, oxidative stress injury.
2. 2. The use of FER1L6 gene in the prevention and treatment of diabetes as claimed in claim 1, wherein said diabetes is type 2 diabetes T2DM.
3. 3. The use of the FER1L6 gene according to claim 1 for the prevention and treatment of diabetes, wherein the lipid metabolism includes but is not limited to triglyceride TG and total cholesterol TC.
4. 4. The use of the FER1L6 gene according to claim 1 for the prevention and treatment of diabetes, wherein the oxidative stress comprises, but is not limited to, superoxide dismutase SOD and malondialdehyde MDA.
5. 5. The use of FER1L6 gene according to claim 1 for preventing and treating diabetes, wherein the inhibition of FER1L6 expression is specifically: RNA interfering molecules or antisense oligonucleotides, small molecule inhibitors, siRNA against FER1L6 are designed to inhibit transcription and expression of FER1L6 by means of lentiviral infection or gene knockout, or specific antibodies against FER1L6 itself or molecules upstream and downstream thereof are designed.
6. 6. The application of the FER1L6 gene in preventing and treating diabetes as claimed in claim 5, wherein when the expression of FER1L6 is inhibited by adopting a virus infection method, the targeting sequence is shown as SEQ ID No.1, specifically: CCGGAAGATTGGAGATAAA.