Alpha-amylase inhibiting peptides and use thereof

Abstract

The application belongs to the field of biopharmacy and relates to an alpha-amylase inhibiting peptide and application thereof. Specifically, the unreported peptide segment LDKFLWT can effectively inhibit alpha-amylase activity, and animal experiments prove that the newly designed polypeptide has the effects of reducing blood sugar, reducing blood lipid, improving insulin resistance and the like; compared with traditional hypoglycemic drugs, the alpha-amylase inhibiting peptide has significant safety.

Description

Technical Field

[0001] This invention belongs to the field of biopharmaceuticals and relates to an α-amylase inhibitory peptide and its applications. Background Technology

[0002] Diabetes mellitus and its related metabolic diseases have become a major public health challenge worldwide, especially type 2 diabetes mellitus (T2DM), whose core characteristics are insulin resistance and postprandial hyperglycemia. Insulin resistance refers to the reduced efficiency of insulin in promoting glucose uptake and utilization, resulting in the ineffective absorption and utilization of glucose by cells, thus causing elevated blood glucose levels. Postprandial hyperglycemia refers to a sharp rise in blood glucose levels after eating. Long-term hyperglycemia can cause serious damage to vital organs such as the cardiovascular system, kidneys, and retina, increasing the risk of diabetic complications. Alpha-amylase rapidly breaks down starch into absorbable sugars, causing a rapid rise in blood glucose levels, affecting glycemic homeostasis, increasing the secretory burden on insulin, and thus exacerbating insulin resistance. Therefore, inhibiting alpha-amylase activity has become one of the important strategies for regulating postprandial blood glucose levels.

[0003] Alpha-amylase inhibitors competitively bind to the active sites of α-amylase in saliva and pancreatic juice, inhibiting starch breakdown and causing undigested carbohydrates to be transferred to the later stages of the intestine for slow-release absorption. This prolongs the glucose absorption timeline and significantly smooths the postprandial blood glucose fluctuation curve. Currently, chemical α-amylase inhibitors such as apocarboxose, voglibose tablets, and miglitol tablets are widely used clinically. Although their hypoglycemic effects are significant, long-term use can lead to weight gain, gastrointestinal discomfort (such as bloating and diarrhea), and potential liver and kidney toxicity. In contrast, α-amylase inhibitory peptides, due to their high safety and strong targeting, have become a hot topic in the research and development of functional hypoglycemic foods and drugs. For example, plant protein functional peptides have shown certain inhibitory activity, but their stability and bioavailability still need improvement. In addition, some inhibitory peptides have low inhibition rates, only about 35%, which limits their application value.

[0004] To improve activity and stability, previous studies have attempted to combine inhibitory peptides with plant polyphenols; however, the compounding process is complex, and the improvement in thermal stability is limited. Although compositional designs (such as the soybean peptide-selenium-enriched yeast system in CN 118403140 A) can enhance hypoglycemic effects through synergistic effects, their formulations are complex. Therefore, there is an urgent need to design a novel short peptide α-amylase inhibitor that combines high inhibitory activity, excellent stability, and multiple physiological functions to promote its widespread application in clinical treatment and functional foods. Summary of the Invention

[0005] To overcome the shortcomings of the prior art, the present invention provides the following technical solution, specifically:

[0006] The first aspect of the present invention is to provide a polypeptide molecule, characterized in that the polypeptide molecule can inhibit α-amylase activity, the polypeptide molecule contains LDKFLWT, and the length of the polypeptide molecule is less than 10 amino acids; preferably, the polypeptide molecule is characterized in that the polypeptide molecule is LDKFLWT.

[0007] A second aspect of the present invention is to provide an α-amylase inhibitor, characterized in that the inhibitor comprises the polypeptide molecule described in the first aspect.

[0008] A third aspect of the present invention is to provide a pharmaceutical composition for treating diabetes, characterized in that the pharmaceutical composition contains the polypeptide molecule described in the first aspect.

[0009] Furthermore, the pharmaceutical composition further includes a pharmaceutically acceptable carrier, and the administration route of the drug includes oral, injection, or gavage.

[0010] Furthermore, the dosage of the polypeptide molecule is 80–120 mg / kg body weight.

[0011] A fourth aspect of the present invention is to provide the use of the polypeptide molecule described in the first aspect in the preparation of a medicament for treating diabetes.

[0012] Furthermore, the pharmaceutical composition further includes a pharmaceutically acceptable carrier, and the administration route of the drug includes oral, injection, or gavage.

[0013] Furthermore, the dosage of the polypeptide molecule is 80–120 mg / kg body weight.

[0014] A fifth aspect of the invention is to provide the use of the polypeptide molecule described in the first aspect in the preparation of a medicament for treating hyperlipidemia.

[0015] Furthermore, the pharmaceutical composition further includes a pharmaceutically acceptable carrier, and the administration route of the drug includes oral, injection, or gavage.

[0016] Furthermore, the dosage of the polypeptide molecule is 80–120 mg / kg body weight.

[0017] The beneficial effects of this invention include:

[0018] 1. The previously unreported peptide LDKFLWT provided in this application has the advantages of being safe, non-toxic, and without side effects. It can effectively inhibit α-amylase activity and regulate postprandial blood glucose, thereby playing a certain role in alleviating diabetes and its complications.

[0019] 2. The α-amylase inhibitory peptide involved in this invention can be used as the core active ingredient, and by adding appropriate excipients, a series of functional products for regulating blood pressure and blood sugar can be prepared. These products can meet diverse drug administration needs and are suitable for patients with type 2 diabetes. Compared with traditional hypoglycemic drugs, the α-amylase inhibitory peptide of this invention has significant safety and no adverse reactions.

[0020] 3. Based on a diabetic mouse model induced by a combination of high-fat diet (HFD) and streptozotocin (STZ), this invention demonstrates through peptide intervention that the newly designed peptide has effects such as lowering blood sugar, lowering blood lipids, and improving insulin resistance. Attached Figure Description

[0021] Figure 1. Molecular docking results: Figure 1A , polypeptide B1; Figure 1B , polypeptide B2; Figure 1C Polypeptide B3; Figure 1D ,Polypeptide B4.

[0022] Figure 2 Results of high performance liquid chromatography of peptides.

[0023] Figure 3 Peptide mass spectrum.

[0024] Figure 4 α-Amylase inhibitory activity.

[0025] Figure 5 Schematic diagram of animal experiments.

[0026] Figure 6 Monitoring the therapeutic effect of peptide intervention on a diabetic mouse model: A, body weight; B, water intake; C, food intake; D, fasting blood glucose; E, OGTT test results; F, area under the OGTT curve; G, ITT test results; H, area under the ITT curve; I, total cholesterol (TC) concentration; J, triglyceride (TG) concentration; K, high-density lipoprotein (HDL-C) concentration; L, alanine aminotransferase (ALT) activity; M, aspartate aminotransferase (AST) activity; N, pancreatic and liver pathological sections. Detailed Implementation

[0027] The following detailed embodiments further illustrate the concept and technical effects of the present invention to fully understand its purpose, features, and effects. Unless otherwise specified, all methods described are conventional methods. Unless otherwise specified, all materials are available from publicly available commercial sources. The illustrative embodiments and descriptions of the present invention are used to explain the invention and do not constitute an undue limitation thereof. It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other.

[0028] Example 1: Design of peptides and analysis of active sites

[0029] Based on a newly designed bioactive peptide sequence, the three-dimensional structure was predicted using the online tool AlphaFold3 (https: / / alphafoldserver.com / ), thus obtaining the peptide's spatial conformation. Then, the high-resolution crystal structure of human α-amylase was obtained from the PDB database (https: / / www.rcsb.org / ) (PDB ID: 1HNY; resolution: [missing information]). The α-amylase protein was identified and designated as the receptor protein. The receptor protein was dehydrated and its co-crystallized ligands and heterologous ions were removed using Discovery Studio. Structural preprocessing, including dehydration and hydrogenation, was performed using the Pymol molecular visualization system to obtain a complete molecular model of the α-amylase protein. In the open-source molecular docking system AutoDock Vina, the preprocessed α-amylase and peptide were defined as the receptor and ligand, respectively, and molecular docking was performed. Based on the docking results, the affinity between the receptor and ligand was analyzed, and the optimal conformation was selected based on the binding free energy (ΔG). The interface characteristics of the peptide ligand-α-amylase receptor were systematically analyzed using Discovery Studio and Pymol. Key binding residues were identified by calculating parameters such as van der Waals surface contact area, hydrogen bond network, salt bridging, and hydrophobic interactions. The amino acid residues forming stable interactions within the binding pocket were visualized and characterized, elucidating the molecular basis for the peptide's inhibition of α-amylase activity. The molecular docking results are shown in Figure 1. FMFPH interacts with amino acid residues of amylase, including Gln63, Leu165, His305, Tyr151, His299, Ala198, and His201, through hydrogen bonds, van der Waals forces, and π-stacking. PFQQWH interacts with amino acid residues of amylase, including Thr163, His201, Asp197, Asp300, His305, Trp58, Leu162, Trp59, and Tyr151, through hydrogen bonds, van der Waals forces, and π-stacking. TPWFF interacts with amino acid residues of amylase, including His201, Ile235, Tyr62, and Leu162, through hydrogen bonds, van der Waals forces, and π-stacking. LDKFLWT interacts with amino acid residues of amylase, such as Thr163, Trp59, His305, Ala307, His201, Tyr151, His299, and Tyr62, through hydrogen bonds, van der Waals forces, and π stacking.

[0030] Example 2: Prediction of peptide bioactivity, toxicity, and physicochemical properties

[0031] Bioactivity was predicted using the online tool PeptideRanker (http: / / distilldeep.ucd.ie / PeptideRanker / ). The results showed that the bioactivity of the four short peptides described in this application was greater than 0.5, indicating they were safe, non-toxic, easily digestible and absorbed, and had the potential to be developed into α-amylase inhibitors. The binding energies of the four short peptides FMFPH, PFQQWH, TPWFF, and LDKFLWT were obtained using AutoDockTools molecular docking software: -8.5 kcal / mol, -9.8 kcal / mol, -8.6 kcal / mol, and -7.4 kcal / mol, respectively. The predicted molecular weights were 677.88 Da, 842.01 Da, 696.86 Da, and 922.19 Da, respectively. Specific peptide prediction results are shown in Table 1.

[0032] Table 1. Results of peptides with good docking effects with α-amylase in virtual screening.

[0033]

[0034] Example 3 Synthesis of Polypeptides

[0035] The peptide synthesis work involved in this application was completed by Nanjing Genscript Biotech Co., Ltd. using solid-phase synthesis (SPPS). All peptide products were verified by high-performance liquid chromatography (HPLC) to have a purity greater than 95%. SPPS involves sequentially coupling amino acids to a resin to form peptide chains. After the sequence synthesis is completed, the N-terminal Fmoc protecting group is deprotected first (after N-terminal modification) and then the side chain protecting group is deprotected to cleave the peptide from the resin. The standardized process is as follows: (1) Resin activation: Take an appropriate amount of modified resin, add the prepared amino acid solution to the resin, and react for a period of time; (2) Fmoc removal: Add Pip / DMF solution for a period of time, and then remove the solvent by vacuum filtration; (3) Washing: Add DMF to the resin (washing step), and remove the solvent by vacuum filtration; (4) Resin detection: Put test reagents A and B and an appropriate amount of resin into a test tube, put the test tube into a high-temperature water bath for 3-5 seconds, and check the color change of the resin. If the color of the resin changes, the Fmoc group has been successfully removed; (5) Amino acid condensation: Add the prepared amino acid solution to the resin. Then add the coupling reagent, shake well for a period of time, and remove the solvent by vacuum filtration; (6) Repeat steps 2-5 until the synthesis of the last amino acid is completed.

[0036] The purity of FMFPH is 96.75%. Figure 2 B1, Table 2), the molecular weight was identified by mass spectrometry as 677.4 Da (B1, Table 2). Figure 3 B1). PFQQWH purity is 99.77% ( Figure 2 B2, Table 3), the molecular weight was identified by mass spectrometry as 842 Da (B2, Table 3). Figure 3 B2). TPWFF purity is 99.83% ( Figure 2 B3, Table 4), the molecular weight was identified by mass spectrometry as 696.5 Da (B3, Table 4). Figure 3 B3). LDKFLWT purity is 95.78% ( Figure 2 B4, Table 5), the molecular weight was identified by mass spectrometry as 922.2 Da (B4, Table 5). Figure 3 (B4). The purity and molecular weight of the oligopeptide synthesized by solid-phase synthesis met the requirements.

[0037] Table 2. Peak List of FMFPH High Performance Liquid Chromatography

[0038]

[0039] Table 3. Peak List of PFQQWH High Performance Liquid Chromatography

[0040]

[0041] Table 4. Peak List of TPWFF High Performance Liquid Chromatography

[0042]

[0043] Table 5. High Performance Liquid Chromatography Peak Table for LDKFLWT

[0044]

[0045] Example 4: In vitro verification of α-amylase inhibitory activity

[0046] Prepare 1 U / mL α-amylase solution and 1% (w / w) starch solution using 20 mmol / L PBS buffer (pH 6.9). Add 20 μL of the 5 mg / mL sample solution and 10 μL of the 1 U / mL α-amylase solution to a centrifuge tube and incubate at 37°C with a shaker for 15 min. Then add 500 μL of the pretreated starch solution to the reaction mixture and incubate at 37°C with a shaker for 5 min. Finally, add 600 μL of DNS reaction stop solution and incubate in a boiling water bath for 15 min. After the reaction is complete, cool to room temperature and measure the absorbance at 540 nm.

[0047] Formula for calculating α-amylase inhibition rate:

[0048]

[0049] The four short peptides described in this invention all exhibit good α-amylase inhibitory activity at a concentration of 5 mg / mL (see [link]). Figure 4Among them, B2:PFQQWH and B4:LDKFLWT both exhibited α-amylase inhibitory activities greater than 50%, demonstrating good hypoglycemic properties. Therefore, two peptides, B2 and B4, with high α-amylase inhibitory activities were obtained for further in vivo screening experiments.

[0050] Example 5 Animal Experiment

[0051] Six-week-old male C57BL / 6J mice (purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.) were selected as experimental subjects. They were acclimatized for three days in an environment of 22±2℃, 50%-60% humidity, and a 12-hour light-dark cycle. Five mice were randomly selected as the normal control group and fed a standard diet. The remaining mice were fed a high-fat diet (Beijing Huafukang Biotechnology Co., Ltd., catalog number: H10060), with a fat content of 60% for energy. During the experiment, mouse weight and blood glucose levels were monitored to ensure the animals were in suitable health for the experiment.

[0052] After 6 weeks of high-fat feeding, mice developed insulin resistance. Streptozotocin (STZ) was dissolved in sodium citrate buffer (pH 4.5) and administered intraperitoneally at a dose of 50 mg / kg for 3 consecutive days. Normal control mice received an equal volume of 0.1 mol / L citrate buffer. 72 hours after the last STZ injection, blood glucose levels were measured in the tail vein using a glucometer. A blood glucose level ≥11.1 mmol / L indicated successful induction of a diabetic model. A schematic diagram of the animal experiment is shown below. Figure 5 As shown in Table 6, the grouping and intervention methods are as follows.

[0053] Table 6. Mouse grouping and intervention methods

[0054]

[0055]

[0056] 1) Sample collection

[0057] During the model construction phase, mice underwent daily tail-pinching adaptation training to reduce stress-induced blood glucose fluctuations caused by blood collection. After 3 weeks of peptide intervention, mice were monitored for 6-hour fasting blood glucose levels, body weight, food intake, and water consumption. The blood collection method was standardized to minimally invasive tail vein puncture.

[0058] This application successfully established a type 2 diabetes mellitus (T2DM) model. Specifically, compared with the normal control group mice, the fasting blood glucose level of the T2DM model group mice was significantly increased. Figure 6 D). As a core pathological feature of T2DM, chronic hyperglycemia leads to weight loss in experimental animals by accelerating protein catabolism and lipid peroxidation (see D). Figure 6A). The body weight of mice in the T2DM model group decreased significantly (p<0.05), while the body weight of mice in the positive control and peptide intervention groups increased significantly compared to the model group (p<0.05), indicating that the peptide preparation can effectively reverse the metabolic emaciation induced by T2DM. After 3 weeks of intervention, the body weight of mice was equal to that of the positive control group. The main symptom of hyperglycemia, polydipsia and polyphagia, was significantly improved in the positive control and peptide intervention groups compared to the model group after peptide intervention (see [link to relevant documentation]). Figure 6 (B and C).

[0059] The results showed that both the positive control group and the peptide B4 group exhibited significant glycemic regulation effects after different intervention regimens. The peptide B4 intervention group showed an effect comparable to that of the positive control group. These results indicate that the peptide B4 of this invention has a significant effect on reducing fasting blood glucose levels in mice with type 2 diabetes mellitus (T2DM).

[0060] 2) GTT, ITT

[0061] After three weeks of peptide intervention, mice underwent an oral glucose tolerance test (OGTT) by gavage with 2 g / kg of 20% glucose solution (with physiological saline as the solvent). Blood glucose levels were measured and recorded at five time points: 0, 30, 60, 90, and 120 minutes.

[0062] At the end of the experiment, the insulin tolerance test (ITT) was conducted. Mice were fasted for 4 hours, and blood was collected from the tail vein to measure the fasting basal blood glucose level. Insulin 0.75 U / kg was injected intraperitoneally, and blood glucose levels were measured at 15, 30, 60, 90 and 120 minutes after injection.

[0063] Changes in GTT and AUC in mice of each experimental group (see [reference]) Figure 6 (E and F). Within 15 minutes of administration of 20% glucose solution, blood glucose levels in all groups of mice rapidly increased and reached their peak. From 15 to 120 minutes, blood glucose levels gradually decreased, eventually returning to near the level at 0 minutes. Compared to the normal control group, the T2DM model group showed a slower decline in blood glucose, and its blood glucose concentration was significantly higher than that of the normal control group within 0-120 minutes (p < 0.05). The glucose tolerance curves of the peptide intervention group and the positive control group showed lower curvature, both lower than those of the T2DM model group within 0-120 minutes. Compared to the normal control group, the AUC of the T2DM model group was significantly increased (p < 0.05). Compared to the T2DM model group, the AUC of both the peptide intervention group and the positive control group was significantly decreased (p < 0.05). The AUC of the positive control group and the peptide B4 intervention group were essentially the same.

[0064] Changes in ITT and AUC in mice of each experimental group (see [reference]). Figure 6(G and H). The normal control group mice had the lowest blood glucose levels, which remained relatively stable over 120 minutes. The T2DM model group mice had the highest blood glucose levels. Compared with the T2DM model group mice, the blood glucose levels in the peptide intervention group and the positive control group were lower than those in the T2DM model group, with the positive control group approaching the normal control group and the peptide B4 intervention group approaching the normal control group. Compared with the normal control group mice, the AUC of the T2DM model group mice was significantly increased (p < 0.05). Compared with the T2DM model group mice, the AUC of both the peptide intervention group and the positive control group mice was significantly decreased (p < 0.05). Specifically, the AUC of the peptide B4 intervention group mice was significantly lower than that of the peptide B2 intervention group (p < 0.05).

[0065] The results showed that peptide intervention significantly improved glucose tolerance and insulin resistance in mice, achieving effects comparable to the positive control. After drug intervention, comparing the blood glucose change curves and area under the curve (AUC) in OGTT and ITT tests in diabetic mice allowed for assessment of the drug's ability to improve glucose metabolism, thus providing a preliminary evaluation of its hypoglycemic effect. The results showed that the AUC in the intervention group and the positive control group was significantly lower than that in the T2DM model group (p<0.01), with the AUC of peptide B4 in the OGTT test being comparable to that of the positive control group. This indicates that the peptide LDKFLWT has a good effect on improving glucose tolerance and enhancing insulin sensitivity.

[0066] 3) Serum-related indicators

[0067] Mouse blood samples were collected in anticoagulant tubes and incubated at room temperature for 2-3 hours. The samples were then centrifuged at 1000×g for 10 minutes at 4℃, and the supernatant pale yellow serum was collected and stored at -80℃ for later use. The levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in each group were measured using Nanjing Jiancheng diagnostic kits, and statistical analysis was performed to determine if there were significant differences between the groups.

[0068] Effects on blood lipid levels in mice, such as Figure 6 I arrive Figure 6As shown in Figure M, the serum TC and TG levels were highest in the T2DM model group mice, at 7.51 mmol / L and 2.53 mmol / L, respectively. Compared with the T2DM model group, these lipids were significantly decreased in the peptide intervention group and the positive control group (p < 0.05). Furthermore, peptide B4 reduced serum TC and TG levels to approximately 5.38 mmol / L and 0.58 mmol / L, respectively. The serum HDL-C level was lowest in the T2DM model group mice, at 0.66 mmol / L. The HDL-C levels in the peptide intervention group and the positive control group were significantly increased compared with the T2DM model group. Similarly, the serum ALT and AST levels were highest in the T2DM model group mice, at 91.54 U / L and 71.72 U / L, respectively. The serum ALT and AST levels in the peptide B4 intervention group and the positive control group mice were significantly lower than those in the T2DM model group (p < 0.05) and approached those in the normal model group mice.

[0069] The results showed that intervention with positive control drugs and peptide B4 could significantly reduce the levels of TC, TG, ALT and AST in mouse serum and increase HDL-C levels, thereby helping to improve dyslipidemia, promote glucose and lipid metabolism balance, and further help improve the symptoms of diabetes.

[0070] 4) Animal experimental pathological sections

[0071] Pathological section preparation: Pancreatic and liver tissues were immersed overnight in 4% paraformaldehyde fixative. The pancreatic and liver samples preserved in the fixative were washed three times with PBS buffer for 10 min each time, followed by gradient elution with 30%, 50%, and 70% ethanol for 5 min each time. The tissues were then embedded, and the dehydration and embedding steps are shown in the table below.

[0072] Table 7. Embedding steps for pancreatic and liver tissues

[0073]

[0074] After embedding, the samples were stored at 4℃ for 1 day before tissue sectioning. Pancreatic and liver paraffin blocks were cut into 5μm paraffin sections and baked at 65℃ for 2 hours in preparation for subsequent staining. The dewaxing procedures for the paraffin sections before staining are shown in the table below:

[0075] Table 8 Dewaxing Procedures for Pancreatic and Liver Sections

[0076]

[0077] All sections were stained with hematoxylin and eosin: ① Stain with hematoxylin solution for 1 min 30 s, then rinse with running tap water for 3 min to turn blue, and finally stop the blueing process with distilled water; ② Rinse quickly with 95% ethanol for 30 s to remove excess stain; ③ Immerse in eosin staining solution for 20 s, then rinse quickly with 95% ethanol for 30 s to remove excess stain; ④ Dehydrate in 95% ethanol and 100% ethanol sequentially, rinsing quickly for 1 min at each stage to prevent discoloration; ⑤ Clear in xylene I and xylene II sequentially, rinsing for 10 min at each stage; ⑥ Mount with neutral resin and allow to dry completely before observation under an optical microscope.

[0078] The staining results of the pancreas and liver of each group of mice are shown in the figure below. Figure 6 N. In the normal control group, the pancreatic islet structure of mice was clear and the cells were neatly arranged. In the T2DM model group, the pancreatic islet structure was disordered and the cells were irregularly arranged. The pancreatic islet structure of mice in the peptide intervention group and the positive control group was improved, and the cells were more neatly arranged. In particular, the pancreatic islet structure of mice in the peptide B4 intervention group and the positive control group was close to normal. Mice in the T2DM model group had severe hepatocellular damage, including focal necrosis, inflammatory cell infiltration, and lipid droplet accumulation. Mice in the normal model group had normal liver structure and hepatocellular morphology. The livers of mice in the peptide intervention group and the positive control group almost recovered to normal, with reduced focal necrosis, inflammatory cell infiltration, and lipid droplet accumulation.

[0079] Based on the combined results of animal experiments, peptide B4 can effectively reverse metabolic weight loss, improve symptoms of polydipsia and polyphagia, delay the progression of diabetes, significantly improve impaired glucose tolerance and insulin resistance, and reduce blood lipids, repair the structure of pancreatic islet cells and hepatocytes, and maintain homeostasis. These results provide new insights into dietary intervention methods for diabetic patients in clinical practice and are of significant importance.

[0080] The embodiments described above are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

Claims

1. A polypeptide molecule, characterized in that, The polypeptide molecule can inhibit the activity of alpha-amylase, and the polypeptide molecule is LDKFLWT.

2. An alpha-amylase inhibitor, characterized in that, The inhibitor comprises the polypeptide molecule in claim 1.

3. The inhibitor of claim 2, wherein The inhibitor further comprises a pharmaceutically acceptable carrier.

4. A pharmaceutical composition for treating diabetes, characterized by, The pharmaceutical composition comprises the polypeptide molecule in claim 1.

5. The pharmaceutical composition of claim 4, wherein, The pharmaceutical composition further comprises a pharmaceutically acceptable carrier, and the administration mode of the medicine comprises oral administration, injection and gavage.

6. The pharmaceutical composition according to claim 4 or 5, characterized in that, The administration dose of the polypeptide molecule is 80-120 mg / kg of body weight.

7. Use of the polypeptide molecule of claim 1 for the manufacture of a medicament for the treatment of diabetes, characterized in that, The administration dose of the polypeptide molecule is 80-120 mg / kg of body weight.

8. Use according to claim 7, characterized in that, The medicine further comprises a pharmaceutically acceptable carrier, and the administration mode of the medicine comprises oral administration, injection and gavage.

9. Use of the polypeptide molecule of claim 1 for the manufacture of a medicament for the treatment of hyperlipidemia, characterized in that, The administration dose of the polypeptide molecule is 80-120 mg / kg of body weight.

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