Use of glycerol monodecanoate in preparing hypoglycemic medicament or functional food

Abstract

Use of glycerol monodecanoate in preparing a medicament for treating hyperglycemia or diabetes or a functional food for assisting in lowering blood glucose associated with hyperglycemia or diabetes. Glycerol monodecanoate reduces blood glucose by promoting the expression of the glucokinase gene and the insulin receptor gene in the liver glycolysis pathway and inhibiting the expression of the phosphoenolpyruvate carboxyl kinase gene and the glucose-6-phosphatase catalytic subunit gene in the gluconeogenesis pathway.

Description

Application of decanoic acid monoglyceride in the preparation of hypoglycemic drugs or functional foods Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to the application of decanoic acid monoglyceride in the preparation of hypoglycemic drugs or functional foods. Background Technology

[0002] Medium-chain fatty acid monoglycerides are monoesters formed from medium-chain fatty acids with a carbon chain length of 8-12 and glycerol. Glycerol monodecanoate (GMD) is an esterification product of decanoic acid (C10) and glycerol, and it is naturally found in coconut oil, palm kernel oil, and camphor seed oil. Its chemical formula is C10. 13 H 26 O4 has a molecular weight of 246.34. Industrial uses of glyceryl monodecanoate include its application as an emulsifier, surfactant, lubricant, and solvent. It is used in cosmetics, food, pharmaceuticals, and plastics industries.

[0003] Medium-chain triglycerides (GMDs) exhibit strong inhibitory effects against common food spoilage bacteria (including bacteria and fungi), demonstrating superior preservative properties compared to general chemical preservatives. They are also safer, broader-spectrum, and more efficient than chemical preservatives. Among them, caprylic acid monoglyceride (C8) and lauric acid monoglyceride (C12) are recognized as effective food emulsifiers and preservatives. Studies have shown that GMDs possess excellent antibacterial and antiviral effects, particularly exhibiting significant inhibitory effects against Campylobacter, Salmonella, and Escherichia coli.

[0004] Medium-chain fatty acids (MCFAs), due to their medium-chain nature, can be directly absorbed from the intestines into the portal vein and then metabolized in the liver. They can act as solubilizers and absorption enhancers, improving the in vivo oral bioavailability of drugs (Medium chain fatty acid metabolism and energy expenditure: Obesity treatment implications; DOI:10.1016 / S0024-3205(97)01143-0). In terms of nutritional metabolism, MFAs can rapidly metabolize and produce energy in the body, playing a good role in regulating metabolism, increasing energy expenditure, and preventing metabolic syndrome. Medium-chain fatty acid monoglycerides possess the characteristics of medium-chain fatty acids, and are digested, absorbed, and metabolized extremely quickly in the body.

[0005] Studies have shown that glycerol monocaprylate has good effects on regulating gut microbiota, modulating inflammation, and increasing short-chain fatty acid content (Glycerol monocaprylate modulates gut microbiota and increases short-chain fatty acid production without adverse effects on metabolism and inflammation; DOI:10.3390 / nu13051427). Glycerol monolaurate has also been shown to alleviate inflammation in mice on a high-fat diet (Novel gut microbiota patterns involved in the attenuation of dextran sodium sulfate-induced mouse colitis mediated by glycerol monolaurate via inducing anti-inflammatory responses; DOI:10.1128 / mBio.02148-21).

[0006] Currently, there is a lack of research on decanoic acid monoglycerides. Exploring and developing the nutritional metabolism regulation function of decanoic acid monoglycerides has practical value and significance. Summary of the Invention

[0007] The purpose of this invention is to provide a food-grade substance that lowers blood sugar and improves insulin resistance, which can be used to prepare drugs for the treatment or adjuvant treatment of hyperglycemia, diabetes and other related diseases, or to prepare health foods that help lower blood sugar.

[0008] To achieve the above objectives, the present invention adopts the following technical solution:

[0009] This invention provides the application of decanoic acid monoglyceride in the preparation of drugs for treating hyperglycemia or diabetes or functional foods that help lower blood sugar.

[0010] Hyperglycemia refers to a blood glucose level that is too high, exceeding the normal range but not meeting the diagnostic criteria for diabetes; it is collectively known as impaired glucose tolerance. Experiments using animal models simulating hyperglycemia induced by a long-term high-fat diet have demonstrated that decanoic acid monoglycerides can significantly and effectively improve the body's glucose tolerance and alleviate hyperglycemia induced by a high-fat diet, with better results than two other medium-chain fatty acid monoglycerides: caprylic acid monoglycerides and lauric acid monoglycerides.

[0011] Furthermore, the hyperglycemia is hyperglycemia induced by damage to insulin β cells or insulin resistance.

[0012] In an animal model experiment simulating type 2 diabetes, this invention found that decanoic acid monoglyceride has a strong ability to lower postprandial blood glucose, with an effect comparable to that of the commonly used hypoglycemic drug metformin.

[0013] Furthermore, the diabetes is type 2 diabetes.

[0014] The main manifestations of diabetes include polydipsia. This invention has found that decanoic acid monoglyceride can significantly reduce water intake in diabetic mice, an effect that differs from metformin and is superior to laurate monoglyceride.

[0015] This invention demonstrates that in high-fat diet animal models and type 2 diabetes animal models, intervention with decanoic acid monoglycerides significantly improves glucose tolerance and insulin tolerance. Serum tests show that decanoic acid monoglycerides significantly reduce blood glucose and insulin levels, significantly increase glucagon-like peptide-1 levels, enhance insulin sensitivity, and improve insulin resistance.

[0016] Mechanistic studies have shown that decanoic acid monoglyceride lowers blood glucose by promoting hepatic glycolysis and inhibiting gluconeogenesis. Gene expression level analysis revealed that decanoic acid monoglyceride can promote the expression of glucokinase gene GCK and insulin receptor gene INSR in the hepatic glycolytic pathway, and inhibit the expression of phosphoenolpyruvate carboxykinase gene PEPCK and glucose-6-phosphatase catalytic subunit gene G6PC in the gluconeogenesis pathway, thereby lowering blood glucose.

[0017] Decanoic acid monoglyceride is naturally found in edible oils and has high biocompatibility, making it a promising candidate for development into a drug or functional food for lowering blood sugar. The decanoic acid monoglyceride provided by this invention is also suitable for use in regulating blood sugar in individuals with a long-term high-fat diet or obese individuals.

[0018] Preferably, the drug is in the form of an oral formulation. The specific dosage is adjusted according to the type and severity of the disease, age, and purpose of administration.

[0019] This invention relates to a drug for lowering blood sugar, using decanoic acid monoglyceride as the active ingredient. The drug contains a pharmaceutically effective dose of decanoic acid monoglyceride. Furthermore, the drug may also contain a suitable drug carrier.

[0020] Specifically, the present invention provides a pharmaceutical composition for treating or adjunctive treating hyperglycemia or diabetes, comprising an effective dose of decanoic acid monoglyceride and a pharmaceutically acceptable carrier.

[0021] The pharmaceutical composition is prepared with glyceryl monodecanoate as the main active ingredient and a pharmaceutically acceptable carrier, and can be formulated according to pharmaceutical preparation methods. The drug can be in liquid formulation form.

[0022] This invention uses decanoic acid monoglyceride as the active ingredient to prepare corresponding functional foods for assisting in lowering blood sugar. It can also be added to food or beverages in the form of food additives to improve the health of users.

[0023] Specifically, this invention provides a functional food for assisting in lowering blood sugar, comprising decanoic acid monoglyceride and food-grade acceptable excipients. The functional food can be formulated into dosage forms such as capsules.

[0024] Another object of the present invention is to provide the use of decanoic acid monoglyceride in the preparation of glucagon-like peptide-1 agonists. Glucagon-like peptide-1 can stimulate insulin secretion, enhance insulin sensitivity, inhibit glucagon secretion, delay gastric emptying, and reduce appetite, thereby reducing blood sugar and weight.

[0025] Terminology Explanation:

[0026] The term "comprising" is an open-ended expression, meaning it includes the contents specified in this invention, but does not exclude other aspects.

[0027] The term "treatment" in some embodiments refers to improving a disease or condition (i.e., slowing, stopping, or alleviating the development of a disease or at least one of its clinical symptoms). In other embodiments, it refers to alleviating or improving at least one bodily parameter, including bodily parameters that may not be perceptible to the subject. In still other embodiments, it refers to regulating a disease or condition physically (e.g., stabilizing perceptible symptoms) or physiologically (e.g., stabilizing bodily parameters) or both. In still other embodiments, it refers to preventing or delaying the onset, flare-up, or worsening of a disease or condition.

[0028] The term "effective dose" refers to the amount of a compound that is sufficient to treat a disease when administered to a subject. The effective dose can vary depending on the severity of the disease and the physical condition, age, weight, and sex of the subject to be treated.

[0029] The term "pharmaceutically or food-acceptable carrier / excipient" refers to any formulation or carrier medium capable of delivering an effective dose of the active substance of the present invention without interfering with the bioactivity of the active substance and without toxic side effects on the host or subject.

[0030] The beneficial effects of this invention are as follows:

[0031] This invention discloses for the first time the functions of decanoic acid monoglyceride in lowering blood glucose and improving insulin resistance. Whether in a simulated long-term high-fat diet or in a type 2 diabetes model, decanoic acid monoglyceride exhibits a significant blood glucose-lowering effect, significantly improves insulin resistance symptoms, increases glucagon-like peptide-1 secretion, activates the expression of genes related to hepatic glycolysis and insulin receptors, and inhibits the expression of genes related to hepatic gluconeogenesis. Especially in type 2 diabetes, the blood glucose-lowering effect of decanoic acid monoglyceride is comparable to metformin, and its effect in regulating glucose tolerance and insulin tolerance is superior to metformin, significantly improving polydipsia and polyphagia. Moreover, decanoic acid monoglyceride is a naturally occurring edible substance with high safety; therefore, it has promising applications in the preparation of drugs for treating hyperglycemia and diabetes or functional foods that help lower blood glucose. Attached Figure Description

[0032] Figure 1 shows the glucose tolerance test of high-fat diet mice in Example 1 at week 15 of feeding. Figure 1A shows the blood glucose change curve within 120 minutes after intraperitoneal injection of glucose; Figure 1B shows the area under the blood glucose change curve within 120 minutes; Figure 1C shows the blood glucose level at minute 0 before glucose injection. In the figures, * indicates significance analysis compared with the low-fat control group (NCD), # indicates significance analysis compared with the high-fat control group (HFD), ** represents p < 0.01, *** represents p < 0.001, # represents p < 0.05, and ### represents p < 0.001.

[0033] Figure 2 shows the changes in serum indicators in mice on a high-fat diet in Example 1. Figure 2A shows serum glucose levels; Figure 2B shows serum insulin levels; Figure 2C shows the insulin resistance index calculated from glucose and insulin levels; and Figure 2D shows serum glucagon-like peptide-1 levels. In the figures, * indicates a significant difference compared to the low-fat control group (NCD), # indicates a significant difference compared to the high-fat control group (HFD), * represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001, # represents p < 0.05, ## represents p < 0.01, and ### represents p < 0.001.

[0034] Figure 3 shows gene expression in the livers of mice fed a high-fat diet in Example 1. Figure 3A shows the expression of the glucokinase gene (GCK); Figure 3B shows the expression of the insulin receptor gene (INSR); Figure 3C shows the expression of the phosphoenolpyruvate carboxykinase gene (PEPCK); and Figure 3D shows the expression of the glucose-6-phosphatase catalytic subunit gene (G6PC). In the figures, * indicates a significant difference compared to the low-fat control group (NCD), # indicates a significant difference compared to the high-fat control group (HFD), * represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001, # represents p < 0.05, and ### represents p < 0.001.

[0035] Figure 4 shows the effects of three medium-chain fatty acid monoglycerides on blood glucose in mice on a high-fat diet in Example 2. Figure 4A shows serum glucose levels; Figure 4B shows serum insulin levels; Figure 4C shows the insulin resistance index calculated from glucose and insulin levels; and Figure 4D shows serum glucagon-like peptide-1 levels. In the figures, # indicates a significant difference compared to the low-fat control group (NCD), * indicates a significant difference compared to the high-fat control group (HFD), $ indicates a significant difference compared to the GMC1600 group, * represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001, # represents p < 0.05, ## represents p < 0.01, ### represents p < 0.001, and $ represents p < 0.05.

[0036] Figure 5 shows the blood glucose trends and water intake of diabetic mice under the influence of GMD and GML. Figures 5A and 5B show the blood glucose trends and average daily water intake of diabetic mice over 10 weeks of feeding (GMD experiment), respectively. In the figures, * indicates a significant difference compared to the normal mouse group (wt / wt), # indicates a significant difference compared to the diabetic mouse control group (db / db), $ indicates a significant difference compared to the metformin group, *** represents p < 0.001, ### represents p < 0.001, $$ represents p < 0.01, and $$$ represents p < 0.001. Figures 5C and 5D show the blood glucose trends and average daily water intake of diabetic mice over 9 weeks of feeding (GML experiment), respectively. In the figures, * indicates a significant difference compared to the normal mouse group (wt / wt), # indicates a significant difference compared to the diabetic mouse control group (db / db), *** represents p < 0.001, and ### represents p < 0.001.

[0037] Figure 6 shows the results of glucose tolerance and insulin tolerance experiments in diabetic mice treated with GMD and GML. Figures 6A to 6D show the glucose tolerance experiment at week 8 and the insulin tolerance experiment (GMD experiment) at week 9 in diabetic mice. Specifically, Figure 6A shows the blood glucose change curve within 120 minutes after intraperitoneal injection of glucose; Figure 6B shows the area under the blood glucose change curve within 120 minutes after intraperitoneal injection of glucose; Figure 6C shows the blood glucose change curve within 120 minutes after intraperitoneal injection of insulin; and Figure 6D shows the area under the blood glucose change curve within 120 minutes after intraperitoneal injection of insulin. * indicates significance analysis compared to the normal mouse group (wt / wt), # indicates significance analysis compared to the diabetic mouse control group (db / db), *** represents p < 0.001, # represents p < 0.05, ## represents p < 0.01, and ### represents p < 0.001. Figures 6E to 6H show the glucose tolerance test (GML) and insulin tolerance test (GML) of diabetic mice at week 7 and week 8, respectively. Specifically, Figure 6E shows the blood glucose change curve within 120 minutes after intraperitoneal injection of glucose; Figure 6F shows the area under the blood glucose change curve within 120 minutes after intraperitoneal injection of glucose; Figure 6G shows the blood glucose change curve within 120 minutes after intraperitoneal injection of insulin; and Figure 6H shows the area under the blood glucose change curve within 120 minutes after intraperitoneal injection of insulin. * indicates a significant difference compared to the normal mouse group (wt / wt), # indicates a significant difference compared to the diabetic mouse control group (db / db), *** represents p < 0.001, ## represents p < 0.01, and ### represents p < 0.001.

[0038] Figure 7 shows the changes in serum indicators in diabetic mice after treatment with GMD and GML. Figures 7A to 7D show the changes in serum indicators in diabetic mice after feeding (GMD experiment). Specifically, Figure 7A shows serum glucose content; Figure 7B shows serum insulin content; Figure 7C shows the insulin resistance index calculated from serum glucose and insulin content; and Figure 7D shows serum glucagon-like peptide-1 content. In the figures, * indicates significance analysis compared with the normal mouse group (wt / wt), # indicates significance analysis compared with the diabetic mouse control group (db / db), $ indicates significance analysis compared with the metformin group, * represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001, # represents p < 0.05, ## represents p < 0.01, ### represents p < 0.001, and $$ represents p < 0.01. Figures 7E to 7H show the changes in serum indicators in diabetic mice after feeding (GML experiment). Specifically, Figure 7E shows serum glucose content; Figure 7F shows serum insulin content; Figure 7G shows the insulin resistance index calculated from serum glucose and insulin content; and Figure 7H shows serum glucagon-like peptide-1 content. In the figures, * indicates a significant difference compared to the normal mouse group (wt / wt), # indicates a significant difference compared to the diabetic mouse control group (db / db), ** represents p < 0.01, *** represents p < 0.001, # represents p < 0.05, and ### represents p < 0.001.

[0039] Figure 8 shows the gene expression in the livers of GMD-treated diabetic mice after feeding. Figure 8A shows the expression of the glucokinase gene (GCK); Figure 8B shows the expression of the insulin receptor gene (INSR); Figure 8C shows the expression of the phosphoenolpyruvate carboxykinase gene (PEPCK); and Figure 8D shows the expression of the glucose-6-phosphatase catalytic subunit gene (G6PC). In the figures, * indicates a significant difference compared to the normal mouse group (wt / wt), # indicates a significant difference compared to the diabetic mouse control group (db / db), and $ indicates a significant difference compared to the metformin group. * represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001, # represents p < 0.05, ## represents p < 0.01, ### represents p < 0.001, and $$ represents p < 0.01. Detailed Implementation

[0040] The present invention will be further described below with reference to specific embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Any modifications or substitutions made to the methods, steps, or conditions of the present invention without departing from the spirit and essence of the invention are within the scope of the invention.

[0041] Unless otherwise specified, the test methods used in the following examples are conventional methods; the materials and reagents used are commercially available unless otherwise specified, including decanoic acid monoglyceride CAS: 26402-22-2, lauric acid monoglyceride CAS: 40738-26-9, and caprylic acid monoglyceride CAS: 26402-26-6.

[0042] The following examples show the composition of a standard feed (g / 100g feed): casein 18.96, L-cysteine ​​0.28, corn starch 29.86, maltodextrin 3.32, sucrose 33.17, cellulose 4.74, soybean oil 2.37, lard 1.90, mineral mixture 2.68, potassium citrate 1.56, vitamin mixture 0.95, choline tartrate 0.19, with a total calorie content of 385 kcal / 100g feed. The high-fat feed composition (g / 100g feed) includes: casein 23.31, L-cysteine ​​0.35, corn starch 8.48, maltodextrin 11.65, sucrose 20.14, cellulose 5.83, soybean oil 2.91, lard 20.68, mineral mixture 3.31, potassium citrate 1.92, vitamin mixture 1.16, and choline tartrate 0.23.

[0043] Example 1: Effects of glyceryl monodecanoate (GMD) on mice on a high-fat diet

[0044] 1. Experimental Grouping

[0045] Thirty-six healthy 4-week-old male C57BL / 6 mice (SPF) from Shanghai Silex Laboratory Animal Co., Ltd. were selected as experimental subjects. After a two-week pre-feeding period, all mice were randomly divided into three experimental groups, with three cages per group and four mice per cage, and housed for 16 weeks. Detailed grouping is as follows:

[0046] Low-fat control group (NCD): fed regular feed, with free access to water daily;

[0047] High-fat control group (HFD): fed a high-fat diet with free access to water daily;

[0048] decanoic acid monoglyceride experimental group (GMD): fed a high-fat GMD diet (containing 1600 mg / kg of GMD on the basis of the above high-fat diet), with free access to drinking water every day.

[0049] 2. Glucose tolerance test

[0050] At week 15, all mice underwent a glucose tolerance test: mice were fasted for 12 hours beforehand, and then injected intraperitoneally with glucose solution at a dose of 2 g / kg body weight. Blood glucose concentrations of each mouse were measured using a glucometer at 0, 30, 60, 90, and 120 minutes, and blood glucose change curves were plotted and the area under the curve was calculated. The results are shown in Figure 1.

[0051] As shown in Figure 1A, after intraperitoneal injection of glucose solution, the blood glucose levels of all mice showed an increasing trend within 30 minutes, and then began to slowly decrease over the following 90 minutes. However, the blood glucose levels of the NCD and GMD groups remained lower than those of the HFD group. As shown in Figures 1B and 1C, the area under the glucose tolerance test curve and the blood glucose level at 0 minutes were significantly lower in the NCD and GMD groups than in the HFD group.

[0052] Long-term high-fat diets induced symptoms of hyperglycemia and insulin resistance in mice. Glucose tolerance test results showed that GMD could significantly improve the response and regulation of blood glucose in mice and reduce hyperglycemia caused by high-fat diets.

[0053] 3. Serum marker test

[0054] Mice were fed for 16 weeks. At the end of the experiment, blood was taken from the orbital cavity of the mice, serum was collected, and the mice were euthanized. Subsequently, the livers of the mice were collected and cryopreserved.

[0055] The blood glucose level in mouse serum was determined using a kit from the Nanjing Jiancheng Biotechnology Institute.

[0056] The levels of insulin and glucagon-like peptide-1 (GLP-1) in mouse serum were measured using an ELISA kit from Wuhan GeneMei Biotechnology Co., Ltd. GLP-1 is an intestinal hormone secreted by L cells in the gut. It can suppress appetite, enhance insulin sensitivity, and regulate blood glucose levels by influencing multiple receptors in the body.

[0057] The insulin resistance index is calculated based on blood glucose and insulin levels using the following formula: Insulin level × Blood glucose concentration / 22.5.

[0058] As shown in Figure 2, compared with the NCD group, the HFD group showed significantly higher serum glucose levels, serum insulin levels, and insulin resistance index (Figures 2A, 2B, and 2C), and significantly lower glucagon-like peptide-1 levels (Figure 2D), indicating that the animal model of hyperglycemia and insulin resistance induced by a high-fat diet was successfully established.

[0059] Compared to the HFD group, the GMD group showed significantly lower serum glucose levels, serum insulin levels, and insulin resistance index (Figures 2A, 2B, and 2C), while the glucagon-like peptide-1 (GMP-1) levels were significantly higher, comparable to those in the NCD group (Figure 2D).

[0060] The results show that GMD can significantly increase glucagon-like peptide-1 in mice on a high-fat diet, reduce blood glucose, and alleviate insulin resistance.

[0061] 4. Liver gene expression detection

[0062] Liver gene expression was detected using real-time quantitative PCR: RNA was extracted from the liver using Trizol, and its concentration and purity were determined using a Nanodrop ND-2000 spectrophotometer. The extracted RNA was then reverse transcribed into cDNA using a reverse transcription kit from Novizan Pharmaceuticals (Nanjing). The expression of glucokinase (GCK), insulin receptor (INSR), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase catalytic subunit (G6PC) genes was detected using Novizan's SYBR fluorescent dye on a LightCycler 480 instrument. Primers used for real-time quantitative PCR are shown in Table 1, and the results are shown in Figure 3.

[0063] Table 1. Primer list for real-time quantitative PCR

[0064]

[0065] GCK is the first rate-limiting enzyme in glucose metabolism, converting glucose into glucose-6-phosphate, the first step in glycolysis and glycogen synthesis. GCK also acts as a glucose sensor, regulating insulin secretion and energy balance. Figure 3A shows that GCK gene expression was significantly lower in the HFD group compared to the NCD group; and significantly higher in the GMD group compared to the HFD group, indicating that GMD intake can accelerate glucose metabolism in high-fat diet mice.

[0066] The INSR gene encodes the insulin receptor, a transmembrane tyrosine kinase that binds to insulin or other ligands, thereby activating the insulin signaling pathway and regulating glucose uptake and release. Figure 3B shows that the INSR gene count in the GMD group was significantly higher than that in the HFD group, indicating that GMD intake significantly activates the insulin receptor gene and promotes insulin's role in regulating blood glucose.

[0067] The PEPCK gene encodes phosphoenolpyruvate carboxykinase, an important enzyme involved in gluconeogenesis that converts oxaloacetate to phosphoenolpyruvate, thereby generating glucose. Similarly, the G6PC gene is a key gene in the gluconeogenesis pathway, encoding the catalytic subunit of glucose-6-phosphatase, a crucial enzyme in glucose homeostasis. Figures 3C and 3D show that, compared to the NCD group, the expression of PEPCK and G6PC genes was significantly increased in the HFD group; and compared to the HFD group, the expression of PEPCK and G6PC genes was significantly decreased in the GMD group, indicating that GMD intake inhibited the expression of PEPCK and G6PC in high-fat diet mice, reducing hepatic gluconeogenesis in these mice.

[0068] Example 2: Effects of three medium-chain fatty acid monoglycerides on blood glucose in mice on a high-fat diet

[0069] 1. Experimental Grouping

[0070] Sixty healthy male C57BL / 6 mice (SPF) aged four weeks from Shanghai Silex Laboratory Animal Co., Ltd. were selected as experimental subjects. After two weeks of pre-feeding, all mice were randomly divided into five experimental groups, with three cages per group and four mice per cage, and were housed for 16 weeks. Detailed grouping is as follows:

[0071] Low-fat control group (NCD): fed regular feed, with free access to water daily;

[0072] High-fat control group (HFD): fed a high-fat diet with free access to water daily;

[0073] Caprylic acid monoglyceride experimental group (GMC): fed with a high-fat GMC diet (containing 1600 mg / kg of GMC), with free access to water daily;

[0074] decanoic acid monoglyceride experimental group (GMD): fed with high-fat GMD diet (containing 1600 mg / kg GMD), with free access to water daily;

[0075] Glyceryl laurate experimental group (GML): fed with high-fat GML diet (containing 1600 mg / kg of GML), with free access to water daily.

[0076] 2. Serum marker test

[0077] Mice were fed for 16 weeks. At the end of the experiment, blood was taken from the orbital cavity of the mice, serum was collected, and the mice were euthanized. Subsequently, the livers of the mice were collected and cryopreserved.

[0078] The blood glucose level in mouse serum was determined using a kit from the Nanjing Jiancheng Biotechnology Institute.

[0079] The levels of insulin and glucagon-like peptide-1 in mouse serum were measured using an ELISA kit from Wuhan GeneMe Biotechnology Co., Ltd. The insulin resistance index was calculated based on blood glucose and insulin levels using the following formula: Insulin level × Blood glucose concentration / 22.5.

[0080] As shown in Figure 4, compared with the NCD group, the HFD group showed significantly higher serum glucose levels, serum insulin levels, and insulin resistance index (Figures 4A, 4B, and 4C), and significantly lower glucagon-like peptide-1 levels (Figure 4D), indicating that the animal model of hyperglycemia and insulin resistance induced by a high-fat diet was successfully established.

[0081] Compared to the HFD group, the serum glucose level, serum insulin level, and insulin resistance index were significantly reduced in the GMD group and the GML group (Figures 4A, 4B, and 4C), while the glucagon-like peptide-1 level was significantly increased, comparable to that in the NCD group (Figure 4D). Among them, the GMD group had the strongest effect in reducing blood glucose and insulin resistance index.

[0082] The results show that GMD can significantly increase glucagon-like peptide-1 in mice on a high-fat diet, reduce blood glucose, and alleviate insulin resistance. Its effect is the most significant among medium-chain fatty acid monoglycerides.

[0083] Example 3: Effects of Glyceryl decanoate (GMD) on diabetic mice

[0084] 1. Twelve C57BLKS / JGpt mice and 36 C57BLKS / JGpt-dbdb mice from Jiangsu Jicui Pharmaceutical Co., Ltd. were selected. The C57BLKS / JGpt-dbdb mice are mutant C57BLKS / JGpt leptin receptor mice, a typical mouse model for type 2 diabetes research. After a one-week pre-feeding period, all mice were randomly divided into four experimental groups, with three cages per group and four mice per cage, and kept for 10 weeks. Detailed grouping is as follows:

[0085] Normal mouse control group (wt / wt): C57BLKS / JGpt mice were fed normal diet and had free access to water every day; they were given control solution (50% PEG400 + 50% physiological saline, administered by gavage at a rate of 5 mL / kg body weight) daily.

[0086] Control group of diabetic mice (db / db): C57BLKS / JGpt-dbdb mice were fed normal diet and had free access to water every day; they were given control solution (50% PEG400 + 50% physiological saline, administered by gavage at a rate of 5 mL / kg body weight) daily.

[0087] Metformin experimental group: C57BLKS / JGpt-dbdb mice were fed a normal diet and had free access to water every day; they were given a dose of 200 mg / kg body weight of metformin solution by gavage every day (200 mg metformin was dissolved in 2.5 mL of PEG400 + 2.5 mL of physiological saline, and gavage was performed at a dose of 5 mL / kg body weight).

[0088] Glyceryl decanoate experimental group (GMD): C57BLKS / JGpt-dbdb mice were fed a normal diet and had free access to water daily. GMD solution was administered by gavage at a dose of 160 mg / kg body weight daily (160 mg GMD was suspended in 2.5 mL of PEG400 + 2.5 mL of physiological saline, and administered by gavage at a dose of 5 mL / kg body weight).

[0089] 2. The mice's postprandial blood glucose levels were measured regularly each week, and their daily water intake was recorded. The results are shown in Figure 5.

[0090] As shown in Figure 5A, during the 10 weeks of feeding, the db / db mouse group consistently exhibited higher blood glucose levels, showing a continuous upward trend with the passage of time, reaching an average blood glucose level above 30 mmol / L in the later stages. The daily blood glucose levels in both the Metformin and GMD experimental groups were significantly lower than those in the db / db mouse group, and both groups maintained a stable blood glucose level throughout the feeding period. Metformin is a well-known hypoglycemic drug used for type 2 diabetes. In diabetic mouse models, the hypoglycemic effect of GMD was comparable to that of metformin.

[0091] Diabetic mice exhibit significant thirst and require large amounts of water. The results in Figure 5B show that GMD significantly reduced the daily water intake of diabetic mice, indicating an improvement in diabetes.

[0092] 3. Glucose tolerance test

[0093] Glucose tolerance tests were conducted on all mice at week 8 of rearing. Mice were fasted for 12 hours beforehand, and then injected intraperitoneally with glucose solution at a dose of 1.5 g / kg body weight. Blood glucose concentrations of each mouse were measured using a glucometer at 0, 30, 60, 90, and 120 minutes, and blood glucose change curves were plotted and the area under the blood glucose change curves were calculated. The results are shown in Figure 6.

[0094] As shown in Figure 6A, after intraperitoneal injection of glucose solution, all mice showed an increasing blood glucose level within 30 minutes, followed by a slow decline over the next 90 minutes. The blood glucose level in the wt / wt group remained consistently low, while the blood glucose levels in the Metformin and GMD groups were consistently lower than those in the db / db mouse group. Furthermore, Figure 6B shows that the area under the glucose tolerance curve in the Metformin and GMD groups was significantly lower than that in the db / db mouse group, with the GMD group showing the lowest area among diabetic mice, exceeding the effect of the metformin group.

[0095] 4. Insulin tolerance test

[0096] Insulin tolerance was tested in all mice at week 9 of rearing: mice were fasted for 12 hours beforehand, and then injected intraperitoneally with insulin at a dose of 2 U / kg body weight. Blood glucose concentrations of each mouse were measured using a glucometer at 0, 30, 60, 90, and 120 minutes, and blood glucose change curves were plotted and the area under the blood glucose change curves were calculated. The results are shown in Figure 6.

[0097] As shown in Figure 6C, after intraperitoneal injection of insulin, the blood glucose levels in diabetic mice showed a brief increase followed by a decrease. Similar to the results of the glucose tolerance test, the blood glucose levels in the Metformin and GMD groups were consistently lower than those in the db / db mouse group. Figure 6D shows that the area under the insulin tolerance curve in the Metformin and GMD groups was significantly lower than that in the db / db mouse group. The GMD group also had the lowest area among diabetic mice, and its effect surpassed that of the metformin group.

[0098] The results of glucose tolerance and insulin tolerance tests show that GMD has a significant effect on blood glucose regulation in diabetic mice, and its effect even exceeds that of metformin, a commonly used hypoglycemic drug.

[0099] 5. Effects of glyceryl monodecanoate (GMD) on serum parameters in diabetic mice

[0100] After 10 weeks of rearing, blood was collected from the orbital sinus of mice, serum was collected, and the mice were euthanized. The livers of the mice were then collected and cryopreserved. Blood glucose levels in the mouse serum were measured using a kit from Nanjing Jiancheng Biotechnology Institute, and insulin and glucagon-like peptide-1 levels were measured using an ELISA kit from Wuhan GeneMe Biotechnology Co., Ltd. The insulin resistance index was calculated based on blood glucose and insulin levels using the following formula: Insulin level × Blood glucose concentration / 22.5. The results are shown in Figure 7.

[0101] As shown in Figures 7A to 7D, compared with the db / db mouse group, the serum glucose level and insulin resistance index of the Metformin experimental group and the GMD experimental group were significantly reduced, while the glucagon-like peptide-1 level was significantly increased; the GMD experimental group significantly reduced serum insulin level, and the glucagon-like peptide-1 level was also significantly higher than that of the Metformin experimental group.

[0102] The results showed that GMD could significantly increase the content of glucagon-like peptide-1 in diabetic mice, reduce blood glucose, and alleviate insulin resistance.

[0103] 6. Liver gene expression detection

[0104] Consistent with the high-fat diet mouse experiment described above, quantitative real-time qPCR was used to detect the expression of glucokinase gene (GCK), insulin receptor gene (INSR), phosphoenolpyruvate carboxykinase gene (PEPCK), and glucose-6-phosphatase catalytic subunit gene (G6PC) in the liver.

[0105] As shown in Figure 8, compared with the db / db mouse group, the expression of the glycolysis gene GCK was significantly increased in the Metformin experimental group and the GMD experimental group (Figure 8A), and the expression of INSR was significantly increased in the GMD experimental group (Figure 8B). At the same time, compared with the db / db mouse group, the expression of the gluconeogenesis genes PEPCK (Figure 8C) and G6PC (Figure 8D) was significantly inhibited in both the Metformin experimental group and the GMD experimental group.

[0106] The results showed that GMD could significantly promote liver glycolysis in diabetic mice, activate the expression of insulin receptor genes, and inhibit the expression of liver gluconeogenesis-related genes, thereby achieving the effect of lowering blood glucose.

[0107] Comparative Example 1: Effects of Glyceryl Laurate (GML) on Diabetic Mice

[0108] 1. Twelve C57BLKS / JGpt mice and 36 C57BLKS / JGpt-dbdb mice from Jiangsu Jicui Pharmaceutical Co., Ltd. were selected. After one week of pre-feeding, all mice were randomly divided into four experimental groups, with three cages per group and four mice per cage, and were housed for nine weeks. Detailed grouping is as follows:

[0109] Normal mouse control group (wt / wt): fed with normal feed and free access to water daily; administered control solution (50% PEG400 + 50% physiological saline, administered by gavage at a rate of 5 mL / kg body weight) daily.

[0110] Control group of diabetic mice (db / db): fed with normal feed and free access to water daily; administered control solution (50% PEG400 + 50% physiological saline, administered by gavage at a rate of 5 mL / kg body weight) daily.

[0111] Metformin experimental group (db / db+Metformin): fed with normal feed and free access to water daily; administered metformin solution by gavage at a dose of 200 mg / kg body weight daily (200 mg metformin dissolved in 2.5 mL of PEG400 + 2.5 mL of physiological saline, administered by gavage at a dose of 5 mL / kg body weight).

[0112] The monoglyceride laurate experimental group (db / db+GML): fed with normal feed and free access to water daily; GML solution was administered by gavage at a dose of 160 mg / kg body weight daily (160 mg GML was suspended in 2.5 mL of PEG400 + 2.5 mL of physiological saline, and administered by gavage at a dose of 5 mL / kg body weight).

[0113] 2. The mice's postprandial blood glucose levels were measured regularly each week, and their daily water intake was recorded. The results are shown in Figure 5.

[0114] As shown in Figure 5C, the db / db mouse group consistently exhibited high blood glucose levels during the 9 weeks of feeding, with a trend of continuous increase in blood glucose over time. The daily blood glucose levels in the Metformin and GML experimental groups were significantly lower than those in the db / db mouse group. Figure 5D shows that GML and metformin significantly reduced the daily water intake of diabetic mice, indicating an improvement in diabetes.

[0115] The results showed that GML could improve daily blood glucose levels and reduce water intake in diabetic mice, but the effect was not as good as metformin. Overall, GML was not as effective as GMD in improving blood glucose levels in diabetic mice.

[0116] 3. Glucose tolerance test

[0117] Glucose tolerance tests were conducted on all mice during week 7 of rearing. Mice were fasted for 12 hours prior to the test, and then injected intraperitoneally with glucose solution at a dose of 1.5 g / kg body weight. Blood glucose concentrations of each mouse were measured using a glucometer at 0, 30, 60, 90, and 120 minutes, and blood glucose change curves were plotted and the area under the curve was calculated. The results are shown in Figure 6.

[0118] As shown in Figure 6E, after intraperitoneal injection of glucose solution, blood glucose levels in all mice showed an increasing trend within 30 minutes. In the subsequent 90 minutes, blood glucose levels in the Metformin and GML groups remained consistently lower than those in the db / db mouse group. Figure 6F shows that the area under the glucose tolerance curve in the Metformin and GML groups was significantly lower than that in the db / db mouse group, with the metformin group showing the lowest area among diabetic mice.

[0119] 4. Insulin tolerance test

[0120] Insulin tolerance tests were conducted on all mice at week 8 of rearing. Mice were fasted for 12 hours beforehand, and then injected intraperitoneally with insulin at a dose of 2 U / kg body weight. Blood glucose concentrations of each mouse were measured using a glucometer at 0, 30, 60, 90, and 120 minutes. Blood glucose change curves were plotted, and the area under the blood glucose change curves was calculated. The results are shown in Figure 6.

[0121] As shown in Figure 6G, after intraperitoneal injection of insulin, the blood glucose levels in the Metformin and GML experimental groups were consistently lower than those in the db / db mouse group. Figure 6H shows that the area under the insulin tolerance curve in the Metformin and GML experimental groups was significantly lower than that in the db / db mouse group, with the metformin experimental group also showing the lowest area among diabetic mice.

[0122] The results of glucose tolerance and insulin tolerance tests show that GML is effective in regulating blood glucose in diabetic mice, but compared with the effect of metformin, its effect on regulating blood glucose in diabetic mice is not as good as that of GMD.

[0123] 5. Effects of Glyceryl Monolaurate (GML) on Serum Indicators in Diabetic Mice

[0124] Nine weeks after feeding, blood was collected from the orbital sinus of mice, serum was collected, and the mice were euthanized. The livers of the mice were then collected and cryopreserved. Blood glucose levels in the mouse serum were measured using a kit from Nanjing Jiancheng Biotechnology Institute, and insulin and glucagon-like peptide-1 levels were measured using an ELISA kit from Wuhan GeneMe Biotechnology Co., Ltd. The insulin resistance index was calculated based on blood glucose and insulin levels using the following formula: Insulin level × Blood glucose concentration / 22.5. The results are shown in Figure 7.

[0125] As shown in Figures 7E to 7H, compared with the db / db mouse group, the serum glucose level and insulin resistance index of the Metformin experimental group and the GML experimental group were significantly reduced, while the glucagon-like peptide-1 level was significantly increased. There was no significant difference in glucagon-like peptide-1 level between the Metformin experimental group and the GML experimental group.

[0126] The results showed that GML could significantly reduce blood glucose, alleviate insulin resistance, and increase glucagon-like peptide-1 (GMP-1) content in diabetic mice, but its effect on increasing GMP-1 content was not as good as that of GMD.

Claims

1. The application of decanoic acid monoglyceride in the preparation of drugs for treating hyperglycemia or diabetes, or in functional foods that assist in lowering blood sugar in patients with hyperglycemia or diabetes, characterized in that, The hyperglycemia mentioned is hyperglycemia induced by insulin resistance; the diabetes mentioned is type 2 diabetes, characterized by polydipsia and a significant decrease in serum glucagon-like peptide-1 levels.

2. The application as described in claim 1, characterized in that, The decanoic acid monoglyceride improves the body's tolerance to glucose and insulin, increases the content of glucagon-like peptide-1, enhances insulin sensitivity, and improves insulin resistance.

3. The application as described in claim 1, characterized in that, decanoic acid monoglyceride lowers blood glucose by promoting the expression of glucokinase and insulin receptor genes in the hepatic glycolysis pathway and inhibiting the expression of phosphoenolpyruvate carboxylkinase and glucose-6-phosphatase catalytic subunit genes in the gluconeogenesis pathway.

4. The application as described in claim 1, characterized in that, The drug is in the form of an oral formulation.

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