Alpha-glucosidase inhibitory peptide and application thereof

Abstract

The invention belongs to the field of biological pharmacy, and relates to an alpha-glucosidase inhibitory peptide and application thereof. Specifically, the provided peptide fragment FPKIPPP which is not reported can effectively inhibit the activity of alpha-glucosidase, and animal experiments prove that the newly designed polypeptide has the effects of reducing blood sugar, reducing blood fat, improving insulin resistance and the like through polypeptide intervention; compared with a traditional hypoglycemic drug, the alpha-glucosidase inhibitory peptide disclosed by the invention has remarkable safety.

Description

Technical Field

[0001] The present invention belongs to the field of biopharmaceuticals and relates to an α-glucosidase inhibitory peptide and application thereof. Background Art

[0002] Diabetes mellitus (DM) is a metabolic disease characterized by elevated blood sugar levels, which is affected by a combination of environmental, genetic, and various other factors. According to the Global Diabetes Atlas released by the International Diabetes Federation in 2021, the number of diabetes patients is expected to reach 693 million in 25 years. Type 2 diabetes mellitus (T2DM) accounts for approximately 90% of all diabetes cases, and its pathogenesis is mainly caused by the body's resistance to the normal effects of insulin. The elevated blood sugar levels associated with diabetes often lead to complications, including cardiovascular and cerebrovascular diseases, sensory neuropathy, liver damage, etc., posing a major threat to personal health.

[0003] α-glucosidase is a common target for the treatment of type 2 diabetes (T2DM). It is a membrane-bound enzyme located on the brush border surface membrane of enterocytes. It promotes glucose release by disrupting the bond between the non-reducing glucosyl residue and the glucosyl oxygen of oligosaccharides. α-glucosidase inhibitors work by weakening α-glucosidase activity, thereby inhibiting the hydrolysis of disaccharides or oligosaccharides. This delays carbohydrate absorption and effectively reduces postprandial hyperglycemia. Currently, α-glucosidase inhibitors have become effective first-line glucose-lowering drugs for the treatment of type 2 diabetes. However, while some α-glucosidase inhibitors, such as acarbose and voglibose, are effective in lowering blood sugar, they are associated with significant intestinal side effects and liver damage, limiting their long-term use. Therefore, the search for safe and effective α-glucosidase inhibitors has become a research hotspot.

[0004] Existing α-glucosidase inhibitors (such as acarbose) suffer from gastrointestinal side effects and insufficient target selectivity, while traditional peptide drug design relies on empirical screening, which is inefficient and has limited accuracy in predicting activity. Furthermore, the use of a single high-fat diet or STZ-induced diabetic animal models often leads to phenotypic instability (e.g., large blood sugar fluctuations, inadequate β-cell damage), and existing studies have incompletely evaluated the metabolic protective effects of peptides (e.g., liver and kidney function, lipid metabolism regulation).

[0005] In recent years, peptide drugs have become a research hotspot due to their high specificity, low toxicity, and modifiability. Traditional peptide separation and purification methods, such as ultrafiltration, macroporous resin adsorption, gel chromatography, reverse-phase high-performance liquid chromatography, and ion exchange chromatography, primarily screen peptides based on their molecular size, charge polarity, solubility, and other physical and chemical properties. This process is complex and time-consuming. With the advancement of science and technology, the development of new bioactive peptides through virtual screening combined with in vitro and in vivo experiments can reduce labor costs, shorten development cycles, and increase the success rate of bioactive peptide identification. Summary of the Invention

[0006] In the present invention, we screened out four peptides that bind to the active center of α-glucosidase with high affinity through computer simulation design combined with molecular docking technology, verified their in vitro inhibitory activity against α-glucosidase, and further screened out an active peptide with high blood sugar lowering potential through a hyperglycemic animal model.

[0007] The first aspect of the present invention is to provide a polypeptide molecule, characterized in that the polypeptide molecule can inhibit the activity of α-glucosidase, the polypeptide molecule comprises FPKIPPP, and the polypeptide molecule length is less than 10 amino acids; preferably, the polypeptide molecule is characterized in that the polypeptide molecule is FPKIPPP.

[0008] The second aspect of the present invention is to provide an α-glucosidase inhibitor, characterized in that the inhibitor comprises the polypeptide molecule described in the first aspect.

[0009] The 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.

[0010] Furthermore, the pharmaceutical composition also includes a pharmaceutically acceptable carrier, and the administration of the drug includes oral administration, injection, and gavage.

[0011] Furthermore, the dosage of the polypeptide molecule is 80 to 120 mg / kg body weight.

[0012] The 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 drug for treating diabetes.

[0013] Furthermore, the pharmaceutical composition also includes a pharmaceutically acceptable carrier, and the administration of the drug includes oral administration, injection, and gavage.

[0014] Furthermore, the dosage of the polypeptide molecule is 80 to 120 mg / kg body weight.

[0015] The fifth aspect of the present invention is to provide the use of the polypeptide molecule described in the first aspect in the preparation of a preparation for lowering blood lipids.

[0016] Furthermore, the pharmaceutical composition also includes a pharmaceutically acceptable carrier, and the administration of the drug includes oral administration, injection, and gavage.

[0017] Furthermore, the dosage of the polypeptide molecule is 80 to 120 mg / kg body weight.

[0018] The beneficial effects of the present invention include:

[0019] 1. The previously unreported peptide FPKIPPP provided in this application has the advantages of being safe, non-toxic, and having no side effects. It can effectively inhibit α-glucosidase activity and regulate postprandial blood sugar, thereby playing a certain role in alleviating diabetes and its complications.

[0020] 2. The α-glucosidase inhibitory peptides of the present invention can be used as core active ingredients and, by adding appropriate excipients, can be prepared into a series of functional products for regulating blood lipids and blood sugar. These products can meet diverse dosing needs and are suitable for patients with type 2 diabetes. Compared with traditional hypoglycemic drugs, the α-glucosidase inhibitory peptides of the present invention have significantly better safety and no adverse reactions.

[0021] 3. The present invention is based on a diabetic mouse model induced by a high-fat diet (HFD) and streptozotocin (STZ). The intervention of the peptide proves that the newly designed peptide has the effects of lowering blood sugar, lowering blood lipids, and improving insulin resistance. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Molecular docking simulation diagram of peptides: A: A1; B: A2; C: A3; D: A4;

[0023] Figure 2 Mass spectra and chromatograms of peptide synthesis;

[0024] Figure 3 In vitro activity determination of peptides and animal experimental intervention: A, in vitro inhibitory enzyme activity of peptides; B, body weight; C, fasting blood glucose; D, total cholesterol; E, triglycerides; F, serum alanine aminotransferase level; G, serum aspartate aminotransferase level; H, serum high-density lipoprotein level; I, low-density lipoprotein level; J, insulin tolerance test (ITT); K, glucose tolerance test (OGTT); L, ITTAUC; M, OGTT AUC; N, food intake; O, water intake; P, pancreatic and liver tissue pathological staining results. DETAILED DESCRIPTION

[0025] The following is a further description of the concept of the present invention and the technical effects produced in conjunction with specific embodiments, so as to fully understand the purpose, features and effects of the present invention. The methods described are all conventional methods unless otherwise specified. The materials described can be obtained from public commercial channels unless otherwise specified. The illustrative embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute undue limitations of the present invention. It should be noted that, unless there is a conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

[0026] Example 1 Peptide Design and Active Site Analysis

[0027] 1) This study used computer-aided drug design combined with molecular docking technology to screen out four peptides with α-glucosidase inhibitory potential from a peptide library.

[0028] First, α-glucosidase was searched from the Protein Data Base (PDB) to obtain the X-ray diffraction crystal structure of α-glucosidase. The structure was processed using Discoverystudio2.5 software to fill in missing residues, optimize the hydrogen bond network, and assign the protonation state of key catalytic residues at pH 7.4 (ProtonateProtein tool) to obtain a complete molecular structure. At the same time, its conserved regions were analyzed and an active conformation model was established to preliminarily determine the active domain. Subsequently, based on the pharmacophore characteristics of natural inhibitors (hydroxyl groups, aromatic rings, and positively charged groups), a virtual library containing 500 peptides was designed and generated using the Peptide Designer module, and conformational sampling was performed using the Conformation Generation tool (retaining 10 low-energy conformations). Molecular docking was performed using AutoDock: After the peptide conformation was pre-processed with Prepare Ligands, the active pocket was defined by the flexible side chains of Asp214 and Glu277 (grid range ), set the Lamarckian genetic algorithm (50 runs, population size 150) to complete high-precision docking, and cluster analysis was performed based on binding free energy (ΔG < -7.0 kcal / mol) and RMSD. The top four candidate peptides were screened; hydrogen bonding and hydrophobic interactions were analyzed using Pose Analysis to exclude steric conflicting sequences. Furthermore, the bioactivity of the peptides was predicted using the Peptide Ranker database (a score > 0.5 was considered the activity threshold), and toxicity was assessed using the ToxinPred online tool. Finally, the docking results were visualized using Discovery Studio's Visualization Tools to verify the hydrogen bonding network and binding mode stability.

[0029] As shown in Table 1, the sequences of polypeptides A1, A2, A3, and A4 are WFQHW, MPGPPYD, QFPRW, and FPKIPPP, respectively, and based on molecular docking analysis, the docking affinities (binding energies) of polypeptides A1, A2, A3, and A4 with α-glucosidase protein crystals are -11.4, -10.7, -10, and -9.4 kcal / moL, respectively, indicating that they have good binding affinity with α-glucosidase and have stable binding ability.

[0030] 2) We analyzed the binding sites and interactions between the active peptide and α-glucosidase. We used the Peptide Ranker database to predict the peptide's bioactivity (a score > 0.5 was considered the activity threshold). Toxicity was assessed using the ToxinPred online tool. Finally, we combined the docking results with the Visualization Tools in Discovery Studio to verify the hydrogen bond network and binding mode stability.

[0031] As shown in Figure 1, in the docking box of polypeptide A1, polypeptide A1 forms traditional hydrogen bonds with the amino acid residues ASN447, GLN439, HIS515, ASN443, and ASN46 of α-glucosidase, forms carbon-hydrogen bonds with ASP440, GLN439, and ASP346, and forms π-alkyl bonds with ALA451 and LYS352; in the docking box of polypeptide A2, polypeptide A2 forms traditional hydrogen bonds with the amino acid residues ASN443 and GLN531 of α-glucosidase, forms carbon-hydrogen bonds with ALA529, ASP40, and SEP44, and forms π-alkyl bonds with TYR41 and ALA514. bond; in the polypeptide A3 docking box, polypeptide A3 forms traditional hydrogen bonds with the amino acid residues ASP40, THR517, THR519, ASN443, ASN447, and GLN439 of α-glucosidase, forms a carbon-hydrogen bond with LYS352, and forms a π-alkyl bond with PRO528; in the polypeptide A4 docking box, polypeptide A4 forms traditional hydrogen bonds with the amino acid residues THR517, SER44, ASN447, and GLN439 of α-glucosidase, forms carbon-hydrogen bonds with ARG450 and ASN447, and forms a π-alkyl bond with LYS352, ALA444, and PRO442.

[0032] In addition, as shown in Table 1, according to bioinformatics prediction, the biological activities of peptides A1, A2, A3, and A4 were 0.982583, 0.721492, 0.975774, and 0.90982, respectively. The toxicity was predicted using the ToxinPred online tool, and the prediction results showed that they were all non-toxic, indicating that the four peptides screened out have application potential and have certain biosafety.

[0033] Table 1 Binding energy, biological activity and toxicity of peptides

[0034]

[0035]

[0036] Example 2 Synthesis, Purity and In Vitro Activity Testing of Polypeptides

[0037] Using the solid phase synthesis method, four polypeptides, A1, A2, A3, and A4, which were screened in the early stage, were synthesized.

[0038] 1. Peptide Synthesis: The peptide sequence was synthesized in C-terminus to N-terminus using the in vitro Fmoc solid-phase method. Dry crude peptides were prepared through amino acid ligation, peptide chain ligation, and peptide chain shearing. The crude peptides obtained by chemical synthesis were purified and analyzed using a high-performance liquid chromatograph coupled with a high-resolution mass spectrometer (purification conditions: mobile phase A was a 0.065% (v / v) trifluoroacetic acid aqueous solution in pure water, mobile phase B was a 0.05% (v / v) trifluoroacetic acid solution in acetonitrile, total flow rate: 1 ml / min, detection wavelength: 220 nm). Peptide synthesis was completed at GenScript Co., Ltd.

[0039] As shown in Table 2 , the actual molecular weights of the synthesized polypeptides A1, A2, A3, and A4 were 802.4, 775.4, 732.8, and 795.00, respectively, which were consistent with the theoretical molecular weights.

[0040] In addition, if Figure 2 As shown in the chromatograms, the synthesized peptides are uniform and highly pure, with only a single chromatographic peak. As shown in Table 2, the purities of the synthesized peptides A1, A2, A3, and A4 are 97.242%, 98.957%, 96.963%, and 96.295%, respectively, making them suitable for in vitro and in vivo experiments.

[0041] Glucosidase Inhibition Assay: Prepare a 4 mg / mL peptide aqueous solution in distilled water. Add 10 μL of the peptide solution and 10 μL of α-glucosidase solution (0.3 U, prepared in 0.1 mol / L phosphate buffer, pH 7.2) to the ELISA plate, mix thoroughly, and incubate at 37°C for 10 min. Then, add 120 μL of 2.5 mmol / L PNPG (p-nitrophenyl-α-D-pyranoglucopyranoside) solution. Incubate at 37°C for 15 min, and terminate the reaction with 50 μL of 0.2 mol / L Na₂CO₃ solution. Measure the absorbance at 405 nm (denoted as Sample A). Replace the sample with buffer solution as a blank. A 4 mg / mL acarbose aqueous solution was used as a positive control. α-glucosidase inhibition activity was calculated as follows: α-glucosidase activity inhibition rate (%) = [(A blank – A sample) / A blank] × 100.

[0042] In vitro activity assay results Figure 3 As shown in Figure A, using acarbose as a positive control, its enzyme inhibitory activity against α-glucosidase was 98.68%. The enzyme inhibitory activities of polypeptides A1, A2, A3, and A4 were 98.68%, 91.3%, 1.98%, 2.18%, and 98.32%, respectively. Among them, the enzyme inhibitory activities of polypeptides A1 and A4 were significantly higher than those of polypeptides A2 and A3, and the inhibitory activity of polypeptide A4 against α-glucosidase was not significantly different from that of acarbose, indicating that polypeptide A4 has an enzyme inhibitory effect similar to that of acarbose.

[0043] Table 2 Synthesis of peptides

[0044] Peptide name Theoretical molecular weight Actual molecular weight purity A1 802.89 802.4 97.242％ A2 775.88 775.4 98.957％ A3 732.84 732.8 96.963％ A4 795.00 795.00 96.295％

[0045] Example 3 Animal Experiment

[0046] A type 2 diabetes mouse model was constructed, and polypeptide A1 and polypeptide A4 were selected for intervention. The alleviating effect of active polypeptides on diabetic mice was evaluated from six perspectives: body weight, fasting blood glucose level, food intake, water intake, serum indicators (total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, high-density lipoprotein and low-density lipoprotein), pathological degree of liver and pancreas, and insulin tolerance and glucose tolerance.

[0047] 1. Mouse Model Construction: Six-week-old C57BL / 6J mice were purchased and acclimated to laboratory conditions (22±2°C, 50±5%, 12-h light / dark cycle) for 7 days. After 7 days, the mice were divided into two groups: one group was fed a regular diet and served as the control group (NC), while the other group was fed a high-fat diet to induce the T2DM model and served as the experimental group. After 6 weeks of high-fat diet, the experimental group was fasted for 12 hours with or without water, and then received three consecutive intraperitoneal injections of streptozotocin (STZ, 70 mg / kg bw). The control group was injected with an equal volume of citrate buffer. Three days after STZ injection, the mice were fasted for 12 hours with or without water, and tail tip blood glucose levels were measured. Mice with fasting blood glucose (FBG) ≥11.1 mmol / L were selected and housed for another week. The remaining mice whose blood glucose levels did not meet the standard were given another intraperitoneal injection of STZ (70 mg / kg bw). Mice were designated as T2DM models when their FBG reached ≥11.1 mmol / L. T2DM model mice were fed a high-fat diet throughout the experimental period.

[0048] 2. Grouping and Dosing: The experimental mice with established T2DM models were randomly divided into four groups based on their blood glucose levels: the diabetes group, the peptide intervention group A1, the peptide intervention group A4, and the acarbose group (positive control). Mice fed with conventional feed served as blank controls.

[0049] 1) Blank control group: gavage with an equal amount of normal saline daily;

[0050] 2) Diabetes group: gavage with an equal amount of normal saline daily;

[0051] 3) Active peptide intervention group A1: Peptide A1 was administered orally at a dose of 100 mg / kg·bw;

[0052] 4) Active peptide intervention group A4: Peptide A4 was administered orally at a dose of 100 mg / kg·bw;

[0053] 5) Acarbose group: Acarbose was administered orally at a dose of 100 mg / kg·bw.

[0054] During the feeding period, mice were given free access to food and water. Body weight and fasting blood glucose (FBG) were recorded every 7 days. Before body weight and FBG measurements, mice were fasted for 12 hours, but not water. On day 28 of the experiment, blood was collected from the eyeballs after a 12-hour fast and placed in an ice-bathed blood collection tube. The tubes were placed in an ice-bath for half an hour and then centrifuged at 4°C (1000g / min for 10 minutes). The upper serum layer was aliquoted and stored frozen at -80°C until further use. After blood collection, mice were sacrificed by cervical dislocation and dissected. Tissues such as the liver, kidney, and pancreas were quickly removed. A portion was quickly frozen in liquid nitrogen and stored at -80°C until further use. The remaining portion was stored in 4% paraformaldehyde for histological analysis.

[0055] 3. Test methods

[0056] 3.1 Fasting blood glucose measurement

[0057] Before the experiment, mice were fasted for 6 hours (with free access to water). Blood glucose levels were measured using a portable blood glucose meter using a tail tip blood sampling method. Before blood collection, the tail tip was wiped to avoid contamination. The tail was gently pressed to promote blood flow. A small amount of whole blood (approximately 1 μL) was dripped into the test area of the test strip, and the stable reading (in mg / dL) was recorded. The measurement was repeated three times for each group, and the average value was calculated. Standards were also used to calibrate the instrument to ensure data reliability.

[0058] 3.2 Glucose tolerance test

[0059] Before the experiment, mice were fasted for 6 hours (with free access to water) and gavage-administered with 20% glucose solution at a dose of 2 g / kg body weight. Blood glucose levels were measured by tail tip blood sampling before administration (0 min) and 15, 30, 60, 90, and 120 min after administration. Data were recorded using a blood glucose meter (calibrated daily), and the area under the curve (AUC) was calculated to assess glucose tolerance.

[0060] 3.3 Insulin tolerance test

[0061] Before the experiment, mice were fasted for 4 hours (with free access to water) and intraperitoneally injected with human regular insulin (0.75 U / kg body weight). Blood glucose levels were measured by tail tip blood sampling before injection (0 min) and 15, 30, 60, 90, and 120 min after injection. Data were recorded using a calibrated blood glucose meter, and insulin sensitivity was assessed using the area under the curve (AUC).

[0062] 3.4 HE staining of tissues

[0063] Fresh liver and pancreatic tissues were fixed in 4% tissue fixative overnight, dehydrated with gradient ethanol (50%, 75% and 95%) and embedded in paraffin. Tissue sections were dewaxed and hydrated and then stained with hematoxylin and eosin (H&E). Images were captured using a light microscope and morphological examination was performed.

[0064] 3.5 Determination of liver function indicators

[0065] Blood samples were collected from mice into anticoagulant tubes, incubated at 4°C for 4 hours, and centrifuged at 1000g for 15 minutes at 4°C. The upper serum layer was aliquoted and stored at -20°C. 50 mg of liver tissue was accurately weighed and added to 500 μL of PBS. A 10% tissue homogenate (w / v) was prepared in an ice-water bath. The homogenate was centrifuged at 2500 rpm for 10 minutes at 4°C. The supernatant was aliquoted and stored at -20°C for further analysis. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured using commercially available kits.

[0066] 3.6 Serum index determination

[0067] Use triglyceride assay kit, total cholesterol assay kit, high-density lipoprotein assay kit and low-density lipoprotein assay kit to detect the corresponding levels in serum.

[0068] 4. Results:

[0069] like Figure 3 As shown in Figure B, the body weight of diabetic mice was significantly reduced compared to the control group, while acarbose, polypeptide A1, and polypeptide A4 could significantly restore the body weight of diabetic mice. The restoration level of polypeptide A4 was significantly higher than that of polypeptide A1, and there was no significant difference between the two and acarbose-induced weight loss effects, indicating that polypeptide A4 has a similar weight-improving effect on diabetic mice as acarbose.

[0070] like Figure 3 As shown in Figure C, the fasting blood glucose levels of diabetic mice were significantly higher than those of the normal control group. Peptide A1 could reduce the fasting blood glucose levels of diabetic mice to a certain extent, while peptide A4 and acarbose could significantly reduce the fasting blood glucose levels of diabetic mice. Among them, the improvement effect of peptide A4 was significantly better than that of acarbose and peptide A1.

[0071] like Figure 3 N and Figure 3 As shown in Figure O, compared with the normal control group, diabetic mice showed polydipsia and polyphagia. Acarbose, polypeptide A1, and polypeptide A4 could alleviate this phenomenon to a certain extent, among which polypeptide A4 had a significantly better improvement effect than acarbose and polypeptide A1.

[0072] like Figure 3 As shown in D, the serum total cholesterol level of diabetic mice was significantly higher than that of the control mice. Acarbose, polypeptide A1 and polypeptide A4 could significantly reduce the serum total cholesterol level, and the improvement effect of polypeptide A4 was significantly better than that of polypeptide A1 and acarbose.

[0073] like Figure 3 As shown in E, the serum triglyceride level of diabetic mice was higher than that of the normal control group. Acarbose, polypeptide A1, and polypeptide A4 could significantly reduce the serum triglyceride level of diabetic mice, and the improvement effect of polypeptide A4 was better than that of the acarbose group.

[0074] like Figure 3 As shown in F, the serum alanine aminotransferase level in the diabetic group was higher than that in the normal control group. The acarbose group, the polypeptide A1 group, and the polypeptide A4 group could significantly reduce the serum alanine aminotransferase level, among which the effect of polypeptide A4 was significantly better than that of polypeptide A1 and acarbose.

[0075] like Figure 3As shown in G, the serum aspartate aminotransferase level of the diabetic mice was significantly higher than that of the control group. The acarbose group, polypeptide A1 group, and polypeptide A4 group could significantly reduce the serum aspartate aminotransferase level. Among them, the improvement effect of polypeptide A4 was significantly better than that of polypeptide A1, and to a certain extent, it was also better than that of acarbose.

[0076] like Figure 3 As shown in H, the serum high-density lipoprotein level of the diabetic mice was significantly lower than that of the normal control group. Acarbose, polypeptide A1 and polypeptide A4 could significantly restore the serum high-density lipoprotein level, and the improvement effect of polypeptide A4 was significantly greater than that of polypeptide A1 and acarbose.

[0077] like Figure 3 As shown in Figure 1, the low-density lipoprotein level in the diabetic mice was significantly higher than that in the normal control group. Acarbose, polypeptide A1, and polypeptide A4 could significantly reduce the low-density lipoprotein level in serum, and the improvement effect of polypeptide A4 was better than that of polypeptide A1 and acarbose.

[0078] like Figure 3 J and Figure 3 As shown in Figure L, the insulin tolerance of diabetic mice was severely impaired, while the acarbose group and polypeptide A4 could improve the insulin tolerance of diabetic mice. The improvement effect of polypeptide A4 was significantly better than that of polypeptide A1, and to a certain extent, better than that of acarbose.

[0079] like Figure 3 As shown in K and 3M, the glucose tolerance of diabetic mice was severely impaired. Acarbose and polypeptide A4 could significantly improve the glucose tolerance of diabetic mice. Among them, the improvement effect of polypeptide A1 was better than that of polypeptide A1, and to some extent, it was better than that of the acarbose group.

[0080] like Figure 3 As shown in Figure 1, compared to the normal group, the pancreatic islets in the diabetic group showed severe atrophy and degeneration, with smaller area, irregular shape, unclear boundaries, fewer insulin cells, and irregular and loosely arranged surrounding β cells. After intervention with active peptides, the damage to the pancreatic tissue was alleviated to varying degrees. The degree of recovery of pancreatic tissue in the peptide A4 and acarbose groups was close to that of the normal group, with a significant increase in the islet area and number of islet cells, and the structure was intact with clear boundaries.

[0081] like Figure 3As shown in Figure 1, the hepatocytes of the normal control mice were morphologically normal and uniform in size, with intact liver tissue structure. However, the hepatocytes of the diabetic mice were swollen, hypertrophic, and structurally disorganized, with indistinct nuclei and numerous vacuoles of varying sizes visible around them. Oral administration of polypeptide A1 had no significant improvement, while both polypeptide A4 and acarbose significantly reduced the vacuoles around the nuclei, returning the hepatocyte structure to normal. Polypeptide A4 also significantly improved the liver function of diabetic mice compared to polypeptide A1. In summary, polypeptide A4 significantly alleviates diabetic symptoms by improving the body weight, food intake, and water intake of mice.

[0082] The embodiments described above are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work shall fall 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 α-glucosidase, the polypeptide molecule contains FPKIPPP, and the polypeptide molecule length is less than 10 amino acids.

2. The polypeptide molecule according to claim 1, characterized in that The polypeptide molecule is FPKIPPP.

3. An α-glucosidase inhibitor, characterized in that The inhibitor comprises the polypeptide molecule according to claim 1 or 2.

4. The inhibitor according to claim 3, characterized in that The inhibitor further includes a pharmaceutically acceptable carrier.

5. A pharmaceutical composition for treating diabetes, characterized in that: The pharmaceutical composition contains the polypeptide molecule according to claim 1 or 2.

6. The pharmaceutical composition according to claim 5, characterized in that The pharmaceutical composition further comprises a pharmaceutically acceptable carrier, and the administration of the drug includes oral administration, injection, and gavage.

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

8. Use of the polypeptide molecule according to claim 1 or 2 in the preparation of a drug for treating diabetes, characterized in that: The dosage of the polypeptide molecule is 80 to 120 mg / kg body weight.

9. The use according to claim 8, characterized in that The medicine also includes a pharmaceutically acceptable carrier, and the administration method of the medicine includes oral administration, injection or gavage.

10. Use of the polypeptide molecule according to claim 1 or 2 in the preparation of a drug for treating hyperlipidemia, characterized in that: The dosage of the polypeptide molecule is 80 to 120 mg / kg body weight.

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