GLP-1 secretion promoter and oral composition containing GLP-1 secretion promoter

Abstract

To provide a GLP-1 secretion promoter capable of rapidly promoting the secretion of endogenous GLP-1, and an oral composition containing the same.SOLUTION: The GLP-1 secretion promoter has a polymerized tea polyphenol as an active ingredient, and the GLP-1 secretion promoting effect is for prevention or improvement of hyperglycemia.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a GLP-1 secretion promoter containing a high molecular weight black tea polyphenol as an active ingredient, and an oral composition containing the GLP-1 secretion promoter. [Background technology]

[0002] The body has a homeostatic mechanism that maintains blood glucose levels at a constant level. Even if blood glucose levels rise after a meal, appropriate insulin secretion quickly returns blood glucose levels to normal. However, when type 2 diabetes develops due to constitution or lifestyle, it becomes difficult to quickly return blood glucose levels to normal after a meal due to reduced insulin secretion from the pancreas or reduced insulin action. Factors that influence the promotion of postprandial insulin secretion include the rise in blood glucose caused by carbohydrates derived from meals, as well as two gastrointestinal hormones known as incretin hormones (GLP-1: glucagon-like peptide-1, GIP: glucose-dependent insulinotropic polypeptide).

[0003] GLP-1 has been reported to promote insulin secretion by acting on pancreatic β cells and inhibit the secretion of the blood glucose-increasing hormone glucagon. Therefore, GLP-1 suppresses postprandial blood glucose levels through these actions. Other known effects of GLP-1 include inhibiting gastric emptying and inducing satiety through afferent vagus nerve stimulation. Because GLP-1 is rapidly degraded in vivo by the incretin-degrading enzyme DPP-4 (Dipeptidyl Peptidase-4), DPP-4 inhibitors, which inhibit the degradation of incretins, are used as first-line treatments for type 2 diabetes in Japan. Furthermore, biostable GLP-1 receptor agonists, which are not affected by DPP-4, are also used as antidiabetic drugs and have recently begun to be used as anti-obesity drugs.

[0004] DPP-4 inhibitors inhibit the degradation of the anti-obesity hormone GLP-1, secreted in response to a meal, thereby increasing the blood concentration of active GLP-1. At the same time, they also inhibit the degradation of endogenous GIP, a known obesity hormone with strong anabolic properties. Therefore, while DPP-4 inhibitors can improve hyperglycemia, they do not have anti-obesity effects. GLP-1 receptor agonists, which have anti-obesity effects, are stable in vivo and act directly on the brain. However, they also affect neurons other than those involved in the anti-obesity effect, causing adverse side effects such as nausea, vomiting, and increased heart rate. Therefore, promoting the secretion of endogenous GLP-1 is considered desirable for preventing and improving glucose metabolism disorders and obesity without side effects. In fact, it has been reported that the rare sugar D-psicose, a zero-calorie sweetener, strongly promotes the secretion of endogenous GLP-1, improving overeating, obesity, and type 2 diabetes. Interestingly, it has been reported that promoting endogenous GLP-1 secretion not only promotes insulin secretion but also has the new function of enhancing insulin action (Non-Patent Document 1), suggesting that promoting endogenous GLP-1 secretion may be able to improve insulin resistance, which is a cause of type 2 diabetes.

[0005] GLP-1 is secreted from enteroendocrine cells in response to ingested nutrients, but in recent years, it has become clear that non-caloric, non-nutrient food ingredients also promote GLP-1 secretion. Such food ingredients are thought to be effective in preventing type 2 diabetes. Examples of such food ingredients include the rare sugar D-psicose (Patent Document 1) and green tea catechin, a type of polyphenol (Patent Document 2). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2017 / 018500 [Patent Document 2] Japanese Patent Application Laid-Open No. 2015-83548 [Non-patent literature]

[0007] [Non-Patent Document 1] Nat.Commun.,2018,9:113 Summary of the Invention [Problem to be solved by the invention]

[0008] As mentioned above, there are several known food ingredients that promote the secretion of endogenous GLP-1, but they are not necessarily satisfactory in terms of immediate effect or effectiveness. Therefore, an objective of the present invention is to provide a GLP-1 secretion-promoting agent that can rapidly promote the secretion of endogenous GLP-1, and an oral composition containing the same. [Means for solving the problem]

[0009] In view of the above problems, the present inventors have conducted extensive research into components that can promote the secretion of endogenous GLP-1. As a result, they have found that high molecular weight black tea polyphenols contained in black tea leaves have the effect of rapidly promoting the secretion of endogenous GLP-1, leading to the completion of the present invention. That is, the present invention encompasses the following: [1] A GLP-1 secretion promoter whose active ingredient is high molecular weight black tea polyphenols. [2] An oral composition containing the GLP-1 secretion promoter described in [1]. [3] The oral composition described in [2], which is for preventing or improving hyperglycemia. [4] The oral composition according to [2], which is for inducing satiety. [Effects of the Invention]

[0010] The GLP-1 secretagogue of the present invention rapidly promotes the secretion of GLP-1 from the gastrointestinal tract and enhances insulin action in peripheral metabolic organs such as the liver, muscle, and fat, thereby suppressing postprandial blood glucose elevation and reducing fasting hyperglycemia in type 2 diabetes. Because the improvement of hyperglycemia according to the present invention does not involve an action mechanism that enhances insulin secretion from the pancreas, it is expected to alleviate the impairment of pancreatic function associated with hyperglycemia and provide a pancreatic protective effect. Furthermore, through its GLP-1 secretion-promoting effect, it is expected to inhibit gastric emptying and induce a feeling of satiety via afferent vagus nerve stimulation. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 shows the results of Test Example 1. [Figure 2] FIG. 2 shows the results of Test Example 2. [Figure 3] FIG. 3 shows the results of Test Example 3. [Figure 4] FIG. 4 shows the results of Test Example 4. DETAILED DESCRIPTION OF THE INVENTION

[0012] In the present invention, the term "GLP-1 secretion promoter" refers to an agent that promotes the secretion of endogenous GLP-1 and increases the blood GLP-1 concentration. The GLP-1 secretion promoter of the present invention is characterized by containing high molecular weight black tea polyphenols as an active ingredient.

[0013] The GLP-1 secretagogue of the present invention is characterized by a short response time until endogenous GLP-1 secretion after oral ingestion, and since the postprandial blood GLP-1 concentration reaches its maximum in a short time, it is expected to rapidly produce physiological responses such as suppression of postprandial blood glucose elevation due to incretin action. Therefore, the GLP-1 secretagogue of the present invention is useful for preventing and ameliorating lifestyle-related diseases such as diabetes.

[0014] Furthermore, the GLP-1 secretion promoter of the present invention can temporarily and quickly lower blood glucose levels without increasing insulin secretion in the pancreas in individuals who are classified as high-normal, borderline, or diabetic based on fasting blood glucose levels, and is therefore expected to reduce the burden on the pancreas, which is in an exhausted state due to hyperglycemia, and contribute to the recovery of weakened pancreatic function.

[0015] Furthermore, by taking the GLP-1 secretagogue of the present invention, a secondary effect can be expected in response to an increase in blood GLP-1 concentration. For example, the secreted GLP-1 stimulates the afferent vagus nerve, which is transmitted to the brain, inducing a feeling of satiety. This effect is expected to suppress overeating and obesity, and therefore the GLP-1 secretagogue of the present invention can be used to prevent and improve overeating and obesity.

[0016] As used herein, "prevention" refers to preventing or delaying the onset of a disease or symptom, or reducing an individual's risk of developing a disease or symptom. "Amelioration" refers to improving a disease, symptom, or condition, preventing or delaying the worsening of a disease, symptom, or condition, or reversing, preventing, or delaying the progression of a disease, symptom, or condition.

[0017] (High molecular weight black tea polyphenols) The "high molecular weight black tea polyphenols" that are the active ingredients in the GLP-1 secretion promoters of the present invention refer to high molecular weight polyphenols that include oligomers (e.g., theasinensins, theaflavins, etc.) formed by oxidative polymerization of catechins (e.g., epicatechin, catechin gallate, catechin gallate, epigallocatechin, gallocatechin, epigallocatechin gallate, and gallocatechin gallate) present in the leaves and stems of the tea plant (Camellia sinensis) by the action of oxidative enzymes during the black tea production process, and compounds (thearubigins) of unknown structure that result from the complex polymerization of these components as fermentation progresses, and are components unique to black tea.

[0018] The active ingredient in the GLP-1 secretagogue of the present invention, high molecular weight black tea polyphenols, refers to components quantified by the HPLC method described below. A single peak consisting of elution of multiple high molecular weight polyphenols can be quantified using free theaflavin as a standard substance (reference: Nutrition, 27, pp. 287-292). Free theaflavin (CAS number: 4670-05-7, molecular formula: C29H24O12, molecular weight: 564.49) is available commercially as a reagent. It can also be obtained by isolation and purification from black tea leaves or by a synthetic method in which catechins are chemically bonded. Other components derived from black tea can be analyzed by known methods.

[0019] High molecular weight black tea polyphenols are contained in black tea leaves (including highly fermented oolong tea) obtained by oxidative fermentation of tea plant leaves and stems, as well as in processed products and extracts thereof. Extracts can be used in the present invention. Extracts are obtained by extracting black tea leaves or other raw materials with water or an organic solvent. Extracts with increased high molecular weight polyphenol content using known methods, such as partitioning between liquid phases or column treatment with an adsorbent, are also suitable for use in the present invention. Other suitable materials for use in the present invention include fresh tea plant leaves and stems, extracts obtained by extracting them, catechin preparations with increased catechin content, and artificially produced high molecular weight polyphenols by oxidative polymerization using enzymes or other methods, using purified catechins as raw materials.

[0020] High molecular weight black tea polyphenols can be obtained, for example, from commercially available black tea leaves. Examples of black tea leaves that can be used include Assam and Darjeeling tea leaves from India, Uva and Dimbula tea leaves from Sri Lanka, and tea leaves from various regions, such as Kenya and Malawi in Africa, China, and Indonesia. From the perspective of increasing blood GLP-1 levels, highly fermented tea leaves with a high content of high molecular weight black tea polyphenols are preferred, such as Assam and Kenyan black tea leaves. In addition to these tea leaves, other black tea extracts that can be used include "Black Tea Extract Powder MN-H10" (manufactured by Mitsui Norin Co., Ltd.), "Black Tea Extract Powder MN-C3" (manufactured by Mitsui Norin Co., Ltd.), the low-caffeine "Black Tea Extract Powder BCL" (manufactured by Mitsui Norin Co., Ltd.), and "Polyphenon-TF35" (manufactured by Mitsui Norin Co., Ltd.), which is high in high molecular weight black tea polyphenols. When the mixture containing high molecular weight black tea polyphenols is a black tea extract, the content of high molecular weight black tea polyphenols in the extract is preferably 10 to 100% (mass %), more preferably 20 to 100%, and even more preferably 30 to 100%. Furthermore, the content of high molecular weight polyphenols in the extract of total polyphenols is preferably 50 to 100%, more preferably 70 to 100%, and even more preferably 80 to 100%. When the content of high molecular weight polyphenols is within this range, it is possible to efficiently promote the secretion of GLP-1 in the blood.

[0021] High molecular weight black tea polyphenols are preferably ingested at a concentration effective for promoting blood GLP-1 secretion or for the purpose of secondary effects via promoting blood GLP-1 secretion. For example, the intake amount is preferably 20 to 2,000 mg / day of high molecular weight black tea polyphenols per adult, more preferably 100 to 1,000 mg / day, and even more preferably 150 to 500 mg / day. This intake amount can be adjusted appropriately based on factors such as body weight, sex, and age. In the present invention, the above amount is preferably administered or ingested one to several times a day, preferably once a day.

[0022] (GLP-1 secretion promoter and oral composition containing GLP-1 secretion promoter) The GLP-1 secretagogue, which contains high molecular weight black tea polyphenols as an active ingredient, aims to increase blood GLP-1 levels and can be incorporated into pharmaceutical preparations, foods and beverages, food supplements, pharmaceuticals, quasi-drugs, or raw materials for preparing these to form oral compositions containing the GLP-1 secretagogue (hereinafter sometimes simply referred to as "oral compositions"). In this specification, oral compositions refer to those that are unlikely to be harmful to human health and that can be taken orally or by administration through the digestive tract in normal social life.

[0023] The food and drink containing the GLP-1 secretagogue is not particularly limited, but specific examples of the food and drink that can be used include tea drinks, coffee drinks, carbonated drinks, fruit drinks, fruit liquors, vegetable drinks, soft drinks, dairy drinks, lactic acid bacteria drinks, energy drinks, sports drinks, soy milk, and other beverages; ice cream, ice milk, lacto ice cream, frozen desserts, yogurt, pudding, jelly, and other desserts; steamed buns, sweet bean paste, caramel, candy, candy tablets, snacks, crackers, biscuits, cookies, pies, chocolate, chewing gum, and other confectioneries; soups such as Japanese soup, Western soup, Chinese soup, and miso soup; bread; jams; seasonings such as mayonnaise and dressing; and retort foods such as retort curry. In addition, the supplement can be made into a powder, granule, tablet, capsule, or other form. Furthermore, foods and beverages containing the GLP-1 secretion promoters of the present invention can be made into functional foods or foods for specified health uses with uses such as "blood sugar lowering effect," "prevention or improvement of diabetes," and "suppression of postprandial blood sugar rise," and can be expressed in functional terms such as "for those concerned about blood sugar levels," "suppression of postprandial blood sugar rise," or "bringing high fasting blood sugar levels closer to normal" in accordance with the guidelines for functional foods.

[0024] When used as a pharmaceutical, the active ingredient can be combined with additives such as pharmaceutically acceptable carriers to form an oral composition primarily intended to promote GLP-1 secretion. Formulations include tablets, granules, fine granules, pills, powders, capsules, lozenges, chewable tablets, and liquids (drinks). It can also be incorporated into pharmaceuticals for other indications. The pharmaceuticals to be incorporated are listed in the Japanese Pharmacopoeia, are not particularly limited as long as they are not contraindicated for high molecular weight black tea polyphenols and can be taken orally. When used as a quasi-drug, desired additives can be added to the active ingredient to form oral liquids, health drinks, vitamin-containing health supplements, and other similar formulations. When incorporated into quasi-drugs, the quasi-drugs to be incorporated are not particularly limited as long as they are designated by the Minister of Health, Labor, and Welfare, are not contraindicated for high molecular weight black tea polyphenols, and can be taken orally. Examples of such formulations include oral liquids, health drinks, and vitamin-containing health supplements. Such medicines and quasi-drugs are effective in preventing and improving various diseases caused by hyperglycemia. [Example]

[0025] <About notation> The actual tests performed are described in detail below. In the description, "%" means "% by mass" unless otherwise specified. Furthermore, the numerical range of "lower limit value to upper limit value" means a numerical range of "not less than the lower limit value and not more than the upper limit value" unless otherwise specified. <Test sample> The test sample was a black tea extract (product name: TF35, manufacturer: Mitsui Norin Co., Ltd.) containing 71.6% high-molecular-weight black tea polyphenols. The control sample was a green tea extract (product name: Polyphenon 70S, manufacturer: Mitsui Norin Co., Ltd.) containing 83.6% catechins. The amount of high-molecular-weight black tea polyphenols in the samples was analyzed using the following method (Reference 1: Nutrition, 27, pp. 287-292). Total polyphenols were measured using the ferric tartrate spectrophotometric method described in the "Seventh Edition of the Standard Tables of Food Composition in Japan, 2015 Edition (Seventh Edition) Analysis Manual and Commentary" (supervised by the Ministry of Education, Culture, Sports, Science and Technology, Kenpakusha, published February 2016). The eight catechins (EC, C, EGC, GC, ECg, Cg, EGCg, GCg) and caffeine were measured using the conditions described in Reference 2 (JP Patent Publication No. 2018-134052). The four theaflavins (TF1, TF2A, TF2B, and TF3) were measured under the conditions described in Reference 3 (JP 2010-35548 A). The measurement results (composition of the components in the tea extract) are shown in Table 1.

[0026] [Analysis conditions for high molecular weight black tea polyphenols (HPLC method)] Standard substance: Free theaflavin (Mitsui Norin Co., Ltd.'s in-house preparation) Equipment: Alliance 2695 Separations Module (Waters) Column: Develosil C30-UG-5 (4.6 mm I.D. x 250 mm, particle size 5 μm, manufactured by Nomura Chemical Co., Ltd.) Column temperature: 40℃ Mobile phase: (A) H2O / MeCN / H3PO4 = 1000 / 25 / 0.5 (volume ratio), (B) MeCN Gradient conditions (binary gradient): 0-8 min; (B) 17%, 8-9.5 min; (B) 17-100%, 9.5-16 min; (B) 100%, 16-17 min; (B) 100-80%, 17-20 min; (B) 80%, 20-21 min; (B) 80%-17%, 21-35 min; (B) 17% ·Flow rate: 1.0mL / min Detection: 280nm ·Injection volume: 7.0μL

[0027] [Table 1]

[0028] <Test Example 1> Effect of increasing blood GLP-1 concentration [method] The effect of high molecular weight black tea polyphenols on increasing blood GLP-1 levels was compared with that of green tea catechins. The black tea extract (high molecular weight black tea polyphenols) and green tea extract (green tea catechins) were dissolved in saline containing 10% ethanol and 10% Tween 80 to a concentration of 27.7 mg / ml (20.0 mg / ml as total polyphenols), and 22.7 mg / ml (20.0 mg / ml as total polyphenols), respectively. Saline containing 10% ethanol and 10% Tween 80 was used as a control. Eight-week-old male C57BL / 6J mice were fasted for 16 hours and then divided into three groups: a group treated with high-molecular-weight black tea polyphenols, a group treated with green tea catechins, and a control group (n = 8 per group). Each solution was administered intragastrically at 10 ml per kg body weight. Blood was collected from the portal vein under isoflurane anesthesia 15, 30, and 60 minutes after administration. Approximately 0.5 ml of collected blood was immediately mixed with a solution containing heparin, aprotinin, and vildagliptin, and centrifuged (4°C, 4000 rpm, 10 minutes) to collect plasma. Plasma GLP-1 concentrations were measured using a measurement kit (GLP-1 Total ELISA Kit, Merck Millipore).

[0029] [result] In the group administered high molecular weight black tea polyphenols, endogenous GLP-1 secretion was rapidly stimulated after administration, resulting in a significant increase in blood GLP-1 concentrations. In contrast, in the group administered green tea catechins, no significant difference in blood GLP-1 concentrations was observed between the control group and the control group within the 1-hour observation period (Figure 1). These results confirm that the structure of polyphenols influences the GLP-1 secretion-stimulating effect, and that high molecular weight polyphenols formed by polymerizing catechins are essential. Furthermore, dissection experiments confirmed the location of high molecular weight black tea polyphenols in the intestine after administration. At 15 minutes after administration, when the effect was observed, high molecular weight black tea polyphenols were found in the upper small intestine. This confirmed that GLP-1 secretion occurs in endocrine cells (L cells) in the upper small intestine, which is thought to be responsible for the rapid effect.

[0030] <Test Example 2> Fasting hyperglycemia reducing effect [method] We investigated the effect of administration of high molecular weight black tea polyphenols on fasting hyperglycemia. Six-week-old male C57BL / 6J mice were fed a high-fat diet (HFD) ad libitum for 19–20 weeks to generate a high-fat diet-induced obesity model mouse (DIO mouse) with elevated fasting blood glucose levels. The high-fat diet used was HFD32 (32% fat by weight; CLEA Japan, Inc.). The above black tea extract was dissolved in saline containing 10% ethanol and 10% Tween 80 at concentrations of 13.8 mg / ml and 27.7 mg / ml. Saline containing 10% ethanol and 10% Tween 80 was used as a control. Thirty-six DIO mice were fasted for four hours, and blood was then drawn. They were then divided into three groups (12 mice each): a group receiving high-molecular-weight black tea polyphenols (total polyphenol doses of 100 mg / kg and 200 mg / kg) and a control group. Each solution was administered intragastrically at 10 ml per kg of body weight. Blood samples were taken 1, 2, 3, and 4 hours after administration. Blood glucose levels were measured using a Glucocard (Arkray, Inc.). Plasma collected from the blood samples 0 to 3 hours later was used to measure plasma insulin concentrations using an ultrasensitive mouse insulin assay kit (Morinaga Biological Science Institute, Inc.).

[0031] [result] DIO mice had a fasting blood glucose level above 200 mg / dL before administration, and were chronically hyperglycemic. In the high-molecular-weight black tea polyphenol-treated groups (100 mg / kg and 200 mg / kg total polyphenols), blood glucose levels were significantly lower than in the control group at 2 and 3 hours after administration, falling below 200 mg / dL at 2 hours (Figure 2(A)). This significant decrease in blood glucose continued up to 3 hours after administration, and the cumulative change at 4 hours after administration was also significantly lower than in the control group (Figure 2(B)). Furthermore, plasma insulin concentrations after administration did not change significantly before and after administration in either the control or high-molecular-weight black tea polyphenol groups, and no significant differences were observed between the groups (Figure 2(C)). Based on the above, it was found that high molecular weight black tea polyphenols can temporarily and quickly lower blood glucose levels in living organisms with chronic hyperglycemia without putting a strain on the pancreas by increasing insulin secretion, and have the effect of alleviating the exhaustion of pancreatic function caused by chronic hyperglycemia.

[0032] <Test Example 3> Verification that the blood glucose lowering effect is due to GLP-1 secretion

[0033] [method] The relationship between the blood GLP-1 concentration increasing effect of administration of high molecular weight black tea polyphenols confirmed in Test Example 1 and the fasting hyperglycemia reducing effect confirmed in Test Example 2 was investigated. The above black tea extract was dissolved in saline containing 10% ethanol and 10% Tween 80 at concentrations of 13.8 mg / ml and 27.7 mg / ml. Saline containing 10% ethanol and 10% Tween 80 was used as a control. Eighteen DIO mice were fed a high-fat diet ad libitum for 23 weeks as in Experimental Example 2. After fasting for 4 hours, blood samples were collected and then divided into three groups: a high-molecular-weight black tea polyphenol treatment group (100 mg / kg and 200 mg / kg total polyphenol doses) and a control group (6 mice each). A GLP-1 receptor inhibitor (Exendin (9-39), GenScript, model number RP10872) was administered intraperitoneally at 600 nmol / 5 ml / kg (Figure 3(A)). Blood samples were then collected 15 minutes after inhibitor administration. Each group received an intragastric administration of either the high-molecular-weight black tea polyphenol solution or a control solution at 10 ml / kg body weight (Figure 3(A)). Blood samples were collected 1, 2, 3, and 4 hours after administration. Blood glucose levels were measured in the collected blood.

[0034] [result] The DIO mice had a fasting blood glucose level of over 200 mg / dL before administration and were chronically hyperglycemic. The blood glucose lowering effect of the administration of high molecular weight black tea polyphenols confirmed in Test Example 2 (Figures 2(A) and (B)) was no longer observed after administration of a GLP-1 receptor inhibitor (Figures 3(A) and (B)). That is, it was confirmed that the blood sugar lowering effect of high molecular weight black tea polyphenols is related to the GLP-1 secretion promoting effect of high molecular weight black tea polyphenols observed in Test Example 1.

[0035] <Test Example 4> Comparative test (effect of administration of catechins on fasting hyperglycemia)

[0036] [method] We investigated the effect of catechin administration on fasting hyperglycemia. The above green tea extract (containing 88.0% total polyphenols and 83.6% catechins) was dissolved in saline containing 10% ethanol and 10% Tween 80 at concentrations of 11.4 mg / ml and 22.7 mg / ml (total polyphenols: 10.0 mg / ml and 20.0 mg / ml). Saline containing 10% ethanol and 10% Tween 80 was used as a control. Thirty-six DIO mice were fed a high-fat diet ad libitum for 21-22 weeks as in Test Example 2, and then fasted for 4 hours to collect blood samples. They were then divided into three groups, each consisting of 12 mice: a green tea catechin treatment group (total polyphenol doses of 100 mg / kg and 200 mg / kg) and a control group. Each solution was administered intragastrically at 10 ml per kg of body weight. Blood samples were collected 1, 2, 3, and 4 hours after administration. Blood glucose levels were measured using a Glucocard (Arkray, Inc.).

[0037] [result] The DIO mice had a fasting blood glucose level of over 200 mg / dL before administration, and were chronically hyperglycemic. As shown in Figure 4, unlike the results of Test Example 2, the green tea catechin-treated group showed no significant difference in blood glucose levels after administration compared to the control group, despite the total polyphenol amounts of 100 mg / kg and 200 mg / kg, which were the same as those in Test Example 2. These results confirmed that the blood glucose-lowering effect of high-molecular-weight black tea polyphenols on chronically hyperglycemic subjects observed in Test Example 2 was influenced by the structure of the polyphenols, and that high-molecular-weight polyphenols formed by polymerizing catechins were essential.

[0038] The results of the Examples showed that high molecular weight black tea polyphenols can lower blood glucose levels in chronically hyperglycemic individuals without increasing insulin secretion from pancreatic β cells, thereby restoring pancreatic function that has been strained by chronic hyperglycemic conditions and being useful in preventing and ameliorating lifestyle-related diseases such as diabetes. This effect is thought to be due to the rapid secretion of endogenous GLP-1 in the upper small intestine after ingestion, which in turn enhances insulin action in peripheral metabolic organs such as the liver, muscle, and fat.

Claims

1. A GLP-1 secretion promoter whose active ingredient is high molecular weight black tea polyphenols.

2. An oral composition comprising the GLP-1 secretion promoter according to claim 1.

3. The oral composition according to claim 2, which is for preventing or ameliorating hyperglycemia.

4. The oral composition according to claim 2, which is for inducing satiety.

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