JP7083420B2 - Glucagon inhibitor, glucagon inhibitor composition and glucagon inhibitor food composition - Google Patents

Description

The present invention relates to a glucagon inhibitor capable of suppressing glucagon, a glucagon-suppressing composition, and a glucagon-suppressing food composition.

Glucagon is a hormone that works with insulin to keep blood sugar levels constant. Glucagon is mainly biosynthesized and secreted by α cells in the islets of Langerhans in the pancreas. Glucagon has an action of increasing blood glucose level by promoting secretion by hypoglycemia and acting on hepatocytes to promote glycogenolysis and gluconeogenesis. Glucagon activates protein kinase A through the production of cAMP in the liver, and finally activates glycogen phosphorylase and lipase, etc. to promote glycogenolysis and gluconeogenesis in the liver.

Glucagonoma is a tumor derived from α cells of the pancreas and overproduces glucagon. It is known that when glucagon is overproduced by glucagonoma, blood glucose level rises and hyperglucagonemia occurs. It is also known to cause necrolytic migratory erythema on the skin as a symptom of glucagonoma.

In order to improve various symptoms related to the secretion of glucagon, it is required to develop a drug having an action of suppressing glucagon.

Patent Document 1 discloses exendin, an exendin agonist, a modified exendin, and a modified exendin agonist as compounds that lower plasma glucagon in a therapeutic subject.

Special Table 2002-538084 Gazette

An object of the present invention is to provide a novel drug having an action of suppressing glucagon.

The present inventors freely ingested a diet containing arctigenin for 9 weeks in mice of a leptin receptor deficiency model. After that, when the blood glucagon concentration of this mouse was measured, it was found that the blood glucagon concentration was lower than that of the control group. We also found that in mice treated with arctigenin, the expression levels of the downstream genes FOXO1, PGC1α, PEPCK and G6Pase promoted by glucagon were lower than those in the control group. The present inventors have completed the present invention based on these findings.

The present invention provides a glucagon inhibitor containing alktigenin and / or alktiin as an active ingredient.

The present invention also provides a glucagon-suppressing composition containing alktigenin and / or alktiin as an active ingredient.

The present invention also provides the above-mentioned glucagon-suppressing composition containing burdock, burdock, burdock sprout or forsythia or an extract thereof containing arktigenin and / or arktiin.

The present invention also provides a glucagon-suppressing food composition containing alktigenin and / or alktiin as an active ingredient.

The present invention also provides the above-mentioned glucagon-suppressing food composition containing burdock, burdock, burdock sprout or forsythia or an extract thereof containing arktigenin and / or arktiin.

The present invention also provides an agent for suppressing the expression of FOXO1, PGC1α or PEPCK, which contains alktigenin and / or alktiin as an active ingredient.

The present invention can provide a novel agent having an action of suppressing glucagon. The glucagon inhibitor, the glucagon-suppressing composition and the glucagon-suppressing food composition of the present invention can treat, improve and prevent various symptoms related to glucagon by suppressing glucagon.

The graph which shows the blood glucagon concentration in the control group and the AG group. The graph which shows the expression level of FOXO1 and PGC1α in the control group and the AG group. The graph which shows the expression level of PEPCK and G6Pase in a control group and an AG group. The graph which shows the time-dependent change of fasting blood glucose in a control group and an AG group.

The present invention provides a glucagon inhibitor and a glucagon inhibitor composition containing arctigenin and / or arctiin as an active ingredient.

As used herein, "suppressing glucagon" means suppressing the production or secretion of glucagon in the pancreas, suppressing the concentration of glucagon in the blood, or suppressing the expression of downstream genes promoted by glucagon. Say. As used herein, "suppressing" glucagon means that the amount of glucagon produced, secreted, or the concentration of glucagon in the blood is higher than that of the control group to which the glucagon inhibitor or the composition for suppressing glucagon of the present invention was not administered. Low or low expression of glucagon downstream genes.

The glucagon inhibitor and the glucagon inhibitor composition of the present invention contain arctigenin and / or arctiin as an active ingredient. Arctigenin and arctiin are one of the diphenylpropanoids (lignans) contained in plants such as burdock. Arctiin is a precursor of arctigenin and is known to be metabolized in vivo to become arctigenin. As the arctigenin and / or arctiin, chemically synthesized arctigenin and / or arctiin may be used, or plant-isolated arctigenin and / or arctiin may be used. Further, as alktigenin and / or alktiin, the plant itself containing alktigenin and / or alktiin or an extract of this plant may be used. Plants containing arctigenin and / or arctiin include, for example, gobo (sprouts, leaves, rhizomes, goboushi), ainocole gyo (flowers, leaves, fruits, rhizomes), chosenrengyo (flowers, leaves, fruits, rhizomes), renkyo (flowers).・ Leaves / Fruits / Rhizome), Sinarengyo (Flowers / Leaves / Fruits / Rhizome), Benibana, Yagurumagiku, American Oniazami, Santorisou (Gibanaazami), Cardon, Gorotsuki thiszami, Aniurocoazami, Sesame, Momijihirugao, Shinchikuhimehagi, Chosen Teika Kazura, Teika Kazura, Munin Teika Kazura, Hime Teika Kazura, Tokyo Chikuto, Keteika Kazura, Ryo Kaou, Oketade, Yamazakura, White Inunazuna, Amaranth, Walnut, Enbaku, Spellta Comgi, Soft Wheat, Mexican Itosugi. Of these, burdock (particularly burdock and burdock sprout) and forsythia (particularly leaves) are preferred because of their high content of arktigenin and / or arktiin. When the plant itself is used, it can be raw or dried and chopped, or dried and powdered.

When using a plant extract as arctigenin and / or arctiin, the extract may be prepared from the plant, for example by the following methods. The extract used in the present invention may be extracted from a plant containing, for example, arctigenin and / or arctiin by two steps, an enzymatic conversion step and an extraction step with an organic solvent.

The enzyme conversion step is a step of enzymatically converting arctiin contained in the plant into arctigenin by β-glucosidase, which is an enzyme inherent in the plant. Specifically, by keeping the dried and cut plants at an appropriate temperature, the endogenous β-glucosidase acts to promote the reaction from arctiin to arctigenin. For example, the plant can be kept at an arbitrary temperature by adding an arbitrary solution such as water to the cut plant and stirring the mixture at a temperature of around 30 ° C (20 to 50 ° C).

The extraction step with an organic solvent is a step of extracting alktigenin and alktiin from a plant using any suitable organic solvent. That is, it is a step of extracting an extract from a plant by adding an appropriate solvent in a state where the content of arctigenin is high by the above-mentioned enzyme conversion step. For example, the appropriate solvent is added to the plant and the extract is extracted by heating and stirring for an appropriate period of time. In addition to heating and stirring, the extract can be extracted using any extraction method known to those skilled in the art, such as heating / reflux, drip extraction, immersion extraction, or pressure extraction.

Since arctigenin is sparingly soluble in water, the yield of arctigenin can be improved by adding an organic solvent. As the organic solvent, any organic solvent can be used. For example, alcohols such as methanol, ethanol and propanol, as well as acetone can be used. In terms of safety, it is preferable to use 30% ethanol as the organic solvent. Distilling off the solvent from the extract gives a paste-like concentrate, and further drying the concentrate gives a dried product.

The glucagon inhibitor and the glucagon inhibitor composition of the present invention can be a preparation in any form. Glucagon inhibitors and compositions for suppressing Glucagon are orally administered formulations such as tablets such as sugar-coated tablets, buccal tablets, coated tablets and chewable tablets; troches; pills; powders; capsules containing hard capsules and soft capsules. It can be a granule; and a liquid agent such as a suspension agent, an emulsion, a syrup agent and an elixir agent.

In addition, the glucagon inhibitor and the glucagon inhibitor composition of the present invention can be used for intravenous injection, subcutaneous injection, intraperitoneal injection, intramuscular injection, transdermal administration, nasal administration, transpulmonary administration, intestinal administration, oral administration and oral administration. It can be a parenteral administration preparation such as transmucosal administration. The glucagon inhibitor and the glucagon inhibitor composition of the present invention can be, for example, an injection, a transdermal absorption tape, an aerosol agent, a suppository and the like.

In addition, the glucagon inhibitor and the glucagon inhibitor composition of the present invention can be provided as an external preparation. The external preparation of the present invention can be a pharmaceutical product, a cosmetic product, or the like. The external preparation of the present invention can be an external preparation for application to the skin, scalp, hair, mucous membranes, nails and the like. External agents include, for example, creams, ointments, liquids, gels, lotions, emulsions, aerosols, sticks, sheet masks, solids, foams, oils and ticks; It includes patches such as agents, plasters, tapes and patches; and sprays.

In addition, the glucagon inhibitor and the glucagon inhibitor composition of the present invention can be in an edible form, such as solid, liquid, granular, granular, powdery, capsule-like, cream-like and paste-like. May be.

The glucagon-suppressing composition of the present invention can be a composition for use in pharmaceuticals, cosmetics, foods and the like. The glucagon-suppressing composition of the present invention may further contain any ingredient commonly used in pharmaceuticals, cosmetics and foods. For example, the glucagon-suppressing composition of the present invention may further contain a pharmaceutically acceptable base, carrier, excipient, binder, disintegrant, lubricant, colorant and the like.

Examples of carriers and excipients used in glucagon-suppressing compositions include lactose, glucose, sucrose, mannitol, dextrin, potato starch, corn starch, calcium carbonate, calcium phosphate, calcium sulfate and crystalline cellulose.

Examples of binders include starch, gelatin, syrup, tragant rubber, polyvinyl alcohol, polyvinyl ether, polyvinylpyrrolidone, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose and the like.

Examples of disintegrants include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium hydrogencarbonate, sodium alginate, sodium carboxymethyl cellulose and calcium carboxymethyl cellulose.

Examples of lubricants include magnesium stearate, hydrogenated vegetable oils, talc and macrogol. As the colorant, any colorant that is allowed to be added to pharmaceuticals, cosmetics and foods can be used.

The composition for suppressing glucagon includes sucrose, gelatin, purified cellulose, gelatin, glycerin, sorbitol, ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinylpyrrolidone, phthalate cellulose acetate, hydroxypropylmethylcellulose phthalate, as required. It may be coated with one or more layers such as methyl methacrylate and methacrylic acid polymer.

In addition, the composition for suppressing glucagon is added with a pH regulator, a buffer, a stabilizer, a preservative, a preservative, a diluent, a coating agent, a sweetener, a fragrance, a solubilizer and the like, if necessary. May be good.

The present invention also provides a pharmaceutical product containing the glucagon-suppressing composition of the present invention. The drug of the present invention can be a drug for suppressing glucagon. In addition, the pharmaceutical products of the present invention can be pharmaceutical products for treating, ameliorating and preventing various symptoms related to glucagon, such as diabetes, hyperglycemia, glucagonoma, glucagon hyperemia and necrolytic migratory erythema. Can be a drug for treating, improving and preventing.

The present invention also provides a glucagon-suppressing food composition containing alktigenin and / or alktiin as an active ingredient. The glucagon-suppressing food composition of the present invention can be configured in the same manner as the above-mentioned glucagon-suppressing agent and glucagon-suppressing composition. The food composition of the present invention can be a food composition for ameliorating or preventing diseases and conditions such as diabetes, hyperglycemia, glucagonoma, glucagon hyperemia and necrolytic migratory erythema.

As used herein, the term "food composition" includes not only general foods and drinks, but also foods for the sick, health foods, functional foods, foods for specified health uses, dietary supplements and supplements. Common foods and drinks include, for example, various beverages, various foods, processed foods, liquid foods (soups and the like), seasonings, energy drinks and confectionery. As used herein, the term "processed food" refers to natural foodstuffs (animals, plants, etc.) that have been processed and / or cooked, such as processed meat products, processed vegetable products, processed fruit products, and frozen foods. Includes retort foods, canned foods, bottled foods and instant foods. The food composition of the present invention may be a food product with a label indicating that it suppresses glucagon. Further, the food composition of the present invention may be provided in a form enclosed in a bag, a container or the like. The bag and container used in the present invention can be any bag and container normally used for food.

The content of glucagonin and / or arctiin in the glucagon inhibitor, the glucagon inhibitor composition and the glucagon inhibitor food composition of the present invention may be any amount as long as it can exert the effect of suppressing glucagon, and the object, purpose and application thereof are as long as they can exert the effect of suppressing glucagon. It can be appropriately set according to the administration method (ingestion method). For example, when given orally to humans, it can preferably contain alktigenin and / or alktiin so that the daily intake is 10-2000 mg.

The present invention also provides an expression inhibitor of FOXO1, PGC1α or PEPCK containing arctigenin and / or arctiin as an active ingredient. FOXO1 is a transcription factor that regulates gluconeogenic enzymes in the liver. PGC1α is a transcriptional coactivator whose expression is increased by glucagon and induces the expression of gluconeogenic enzymes in cooperation with FOXO1 and the like. PEPCK is one of the gluconeogenic enzyme genes in the liver.

As used herein, "suppressing expression" means, for example, reducing the amount of transcript of a gene encoding a protein, reducing the amount of protein, and the like.

The FOXO1, PGC1α or PEPCK expression inhibitor of the present invention may contain arktigenin and / or alktiin as burdock, burdock, burdock sprout or forsythia or an extract thereof. Further, the expression inhibitor of FOXO1, PGC1α or PEPCK of the present invention can be configured in the same manner as the above-mentioned glucagon inhibitor, glucagon inhibitor composition and glucagon inhibitor food composition of the present invention.

The FOXO1, PGC1α or PEPCK expression inhibitor of the present invention can suppress the expression of gluconeogenic enzymes and the like by suppressing the expression of FOXO1, PGC1α and / or PEPCK. Therefore, since the FOXO1, PGC1α or PEPCK expression inhibitor of the present invention can suppress gluconeogenesis in the liver, various glucagon-related symptoms such as diabetes, hyperglycemia, glucagonoma, glucagon hyperemia and Necrolytic migratory erythema can be treated, prevented or ameliorated.

Examples are shown below, and embodiments of the present invention will be described in more detail, but the present invention is not limited to the following examples.

(Measurement of enzyme activity)
The β-glucosidase activity in burdock was measured by the following method. Burdock from different production areas and lots was crushed with a Willey crusher, and 0.1 g of this burdock crushed product was diluted with 10 mL of water to prepare a sample solution.

As a substrate solution, water was added to 0.15 g of p-nitrophenyl-β-D-glucopyranoside and the volume was adjusted to 25 mL to prepare a 20 mmol / L p-nitrophenyl-β-D-glucopyranoside aqueous solution. A reaction mixture was prepared by adding 0.5 mL of a 20 mmol / L p-nitrophenyl-β-D-glucopyranoside aqueous solution to 1 mL of 0.1 mol / L acetate buffer, and preheating was performed at 37 ° C. for about 5 minutes.

After adding 0.5 mL of the sample solution to the reaction mixture and reacting at 37 ° C. for 15 minutes, 2 mL of 0.2 mol / L sodium carbonate aqueous solution, which is a reaction stop solution, was added to stop the reaction. The absorbance of this solution at 400 nm was measured, and the enzyme activity was determined by the following formula from the amount of change from the blank solution in which the enzyme reaction was not performed.
Enzyme activity (U / g) = (absorbance of sample solution-absorbance of blank solution) x 4 mL x 1 / 18.1 (mmol molecule extinction coefficient of p-nitrophenol under the above measurement conditions: cm ² / μmol) x 1 / Optical path length (cm) x 1 / reaction time (minutes) x 1 / 0.5 mL x 1 / sample solution concentration (g / mL).

(Example 1 Production of burdock extract 1)
As an example of the glucagon-suppressing composition of the present invention, an extract (extract) was extracted from burdock. Burdock (enzyme activity 8.23 U / g) was cut and passed through a 9.5 mm sieve and further passed through a 0.85 mm sieve, and it was confirmed that 75% remained. 80 kg of this burdock shredded was added to 560 L of water kept at 29 to 33 ° C, and stirred for 30 minutes. Then, 265 L of ethanol was added, the temperature was raised to 85 ° C., and the mixture was heated under reflux for another 60 minutes. This solution was centrifuged to obtain a burdock extract. The extracts obtained by repeating this operation twice were combined, concentrated under reduced pressure, 25% of dextrin was added to the solid content of the extract, and the mixture was spray-dried. The contents of arktigenin and alktiyne were 6.2% and 7.1%, respectively, and burdock extract powder (containing 20% dextrin) having arktigenin / alktiin (weight ratio) = 0.89 was obtained.

(Example 2 Production of burdock extract 2)
As an example of the glucagon-suppressing composition of the present invention, an extract (extract) was extracted from burdock. Burdock (enzyme activity 8.23 U / g) was cut and passed through a 9.5 mm sieve and further passed through a 0.85 mm sieve, and it was confirmed that 75% remained. 80 kg of this burdock shredded was added to 560 L of water kept at 30 to 33 ° C. and stirred for 30 minutes, then 265 L of ethanol was added to raise the temperature to 85 ° C., and the mixture was heated under reflux for another 30 minutes. This solution was centrifuged to obtain a burdock extract. The extracts obtained by repeating this operation twice were combined, concentrated under reduced pressure, 25% of dextrin was added to the solid content of the extract, and the mixture was spray-dried. The contents of arktigenin and alktiyne were 6.0% and 6.8%, respectively, and burdock extract powder (containing 20% dextrin) having arktigenin / alktiin (weight ratio) = 0.87 was obtained.

(Example 3 Production of burdock extract 3)
As an example of the glucagon-suppressing composition of the present invention, an extract (extract) was extracted from burdock. Burdock (enzyme activity 7.82 U / g) was cut and passed through a 9.5 mm sieve and further passed through a 0.85 mm sieve, and it was confirmed that 75% remained. 80 kg of this burdock shredded was added to 560 L of water kept at 30 to 32 ° C. and stirred for 40 minutes, and after 60 minutes, 258 L of ethanol was added to raise the temperature to 85 ° C., and the mixture was heated under reflux for another 30 minutes. This solution was centrifuged to obtain a burdock extract. The extracts obtained by repeating this operation twice were combined, concentrated under reduced pressure, 25% of dextrin was added to the solid content of the extract, and the mixture was spray-dried. The contents of arktigenin and alktiyne were 6.2% and 6.7%, respectively, and burdock extract powder (containing 20% dextrin) having arktigenin / alktiin (weight ratio) = 0.93 was obtained.

(Example 4 Production of burdock extract 4)
As an example of the glucagon-suppressing composition of the present invention, an extract (extract) was extracted from burdock. Burdock (enzyme activity 7.82 U / g) was cut and passed through a 9.5 mm sieve and further passed through a 0.85 mm sieve, and it was confirmed that 75% remained. 80 kg of this burdock shredded was added to 560 L of water kept at 30 to 32 ° C. and stirred for 30 minutes, then 253 L of ethanol was added to raise the temperature to 85 ° C., and the mixture was heated under reflux for another 40 minutes. This liquid was centrifuged to obtain the obtained extract. The extracts obtained by repeating this operation twice were combined, concentrated under reduced pressure, 25% of dextrin was added to the solid content of the extract, and the mixture was spray-dried. The contents of arktigenin and alktiyne were 6.4% and 7.2%, respectively, and burdock extract powder (containing 20% dextrin) having arktigenin / alktiin (weight ratio) = 0.89 was obtained.

(Example 5 Production of Forsythia viridis leaf extract 1)
As an example of the glucagon-suppressing composition of the present invention, an extract (extract) was extracted from the leaves of Forsythia viridis. 350 mL of water was added to 50 g of forsythia leaf chopped containing 2.53% of arctiin and 0.76% of arctigenin, and the mixture was kept warm at 37 ° C. for 30 minutes, then 150 mL of ethanol was added and extracted by heating for 30 minutes. This solution was solid-liquid separated using a 100-mesh sieve and freeze-dried to obtain 18.62 g of Forsythia viridis leaf extract having an arctigenin content of 5.62%.

(Example 6 Production of Forsythia viridis leaf extract 2)
As an example of the glucagon-suppressing composition of the present invention, an extract (extract) was extracted from the leaves of Forsythia viridis. Forsythia leaf chopped 720 g containing 7.38% alktiyne and 0.78% alktigenin were added with 5 L of water and kept warm at 37 ° C for 30 minutes, then 2.16 L of ethanol was added and heat-extracted for 30 minutes. This solution was solid-liquid separated using a 100-mesh sieve and freeze-dried to obtain 343.07 g of Forsythia viridis leaf extract having an arctigenin content of 9.55%.

(Example 7 Granules containing burdock extract powder)
As an example of the glucagon-suppressing composition of the present invention, granules were produced using burdock extract. Granules were manufactured according to the "Japan Bureau" general rules for formulations and the section on granules. That is, the following components (1) to (3) were taken and made into granules. 1.5 g of this was filled in an aluminum laminated film to obtain granules containing 0.5 g of burdock extract powder per packet.

(1) Burdock extract powder of Example 2 33.3%
(2) Lactose 65.2%
(3) Hydroxypropyl cellulose 1.5%
100% in total

(Example 8 Granules containing burdock extract powder)
As an example of the glucagon-suppressing composition of the present invention, granules were produced using burdock extract. Granules were manufactured according to the "Japan Bureau" general rules for formulations and the section on granules. That is, the following components (1) to (3) were taken and made into granules. 3.0 g of this was filled in an aluminum laminated film to obtain granules containing 2 g of burdock extract powder per packet.

(1) Burdock extract powder of Example 2 66.7%
(2) Lactose 30.3%
(3) Hydroxypropyl cellulose 3.0%
100% in total

(Example 9 burdock extract powder-blended tablet)
As an example of the glucagon-suppressing composition of the present invention, tablets were produced using burdock extract. Tablets were prepared according to the "Japan Bureau" general rules for formulations and the section on tablets. That is, the following components (1) to (6) were taken to obtain tablets.

(1) Burdock extract powder of Example 2 37.0%
(2) Crystalline cellulose 45.1%
(3) Carmellose calcium 10.0%
(4) Cross popidone 3.5%
(5) Hydrous silicon dioxide 3.4%
(6) Magnesium stearate 1.0%
100% in total

(Example 10 Effect of arctigenin on blood glucagon and downstream gene expression)

[Experimental animals]
Experiments started after 1 week of pre-breeding using 5-week-old male db / db mice (BKS.Cg- + Leprdb / + Leprdb / Jcl, purchased from Claire Japan), which is a leptin receptor deficiency model. did. Animals were bred in a 12-hour light-dark cycle environment with a temperature of 23.0 ± 5 ° C and a humidity of 50.0 ± 10%. Animal experiments were conducted based on the Keio University Animal Experiment Regulations with the approval of the Keio University Animal Experiment Committee.

[experimental method]
After pre-breeding, the mice were divided into two groups (a) Control group and (b) Arctigenin-administered group (AG group) (n = 8 in each group), and the control group was given a purified feed (AIN-93G) and the AG group. Was allowed to freely ingest a purified feed containing 0.2% of arctigenin (> 98.0%) for 9 weeks. After the administration was completed, the patient was fasted for 18 hours, blood was collected from the abdominal vena cava under anesthesia, and the liver was collected.

[Measurement of blood glucagon concentration]
Blood glucagon concentration was measured using Mercodia Glucagon ELISA Kit (Mercodia AB). FIG. 1 shows the blood glucagon concentration in each group. In the AG group, the blood glucagon concentration was lower than that in the Control group.

[Expression level of downstream genes]
For each group, total RNA was extracted from the obtained organs and cDNA was synthesized, and then the expression levels of the glucagon downstream genes FOXO1, PGC1α, PEPCK, and G6Pase were compared by qPCR. 18S rRNA was used as a control. Primers for qPCR are 18S (F: TTCTGGCCAACGGTCTAGACAAC (SEQ ID NO: 1), R: CCAGTGGTCTTGGTGTGCTGA (SEQ ID NO: 2)), FOXO1 (F: CACACAGCTGGGTGTCAGGCTA (SEQ ID NO: 3), R: GGGGTGAAGGGCATCTTT (SEQ ID NO: 4)), PGC1α. (F: AAGGGCCAAACAGAGAGAGAGA (SEQ ID NO: 5), R: GCGTTGTGTCAGGTCTGATT (SEQ ID NO: 6)), PEPCK (F: GGGAACTGACTACTCGGGAA (SEQ ID NO: 7), R: GCCAGGTATTTCTTCTTGCC (SEQ ID NO: 8)) ), R: TAGCAGGTAGAATCCAAGCGCGAAAC (SEQ ID NO: 10)).

FIG. 2 shows the expression levels of FOXO1 and PGC1α in each group, and FIG. 3 shows the expression levels of PEPCK and G6 Pase. In the AG group, the expression levels of these four genes were lower than in the Control group.

These results suggest that arctigenin has an action of suppressing glucagon.

(Example 11 Changes in fasting blood glucose over time)
For the Control group and the AG group of Example 10, each group was fed with its own food and fasted at the 4th week, and the change over time of fasting blood glucose from the start of fasting was measured. Fasting blood glucose was collected from the tail vein and measured with a self-glucose meter "LIFE CHECK" (EIDIA Co., Ltd.).

FIG. 4 is a graph showing changes over time in fasting blood glucose of each group. In the AG group, the increase in blood glucose was suppressed 16 to 20 hours after fasting as compared with the Control group. Therefore, it was suggested that arctigenin suppresses the increase in blood glucose during fasting by suppressing glucagon.

The present invention can be suitably used for pharmaceuticals and foods for suppressing glucagon.

Claims (8)

A pharmaceutical composition for treating, ameliorating and preventing glucagonoma, which comprises alktigenin and / or alktiin as an active ingredient. A pharmaceutical composition for treating, ameliorating and preventing glucagon hyperemia, which comprises alktigenin and / or alktiin as an active ingredient. A pharmaceutical composition containing necrolytic migratory erythema as an active ingredient, for treating, ameliorating and preventing necrolytic migratory erythema. The pharmaceutical composition according to any one of claims 1 to 3, which comprises the burdock, burdock, burdock sprout or forsythia, or an extract thereof, containing the arktigenin and / or arktiin. A food composition for improving and preventing glucagonoma, which contains alktigenin and / or alktiin as an active ingredient. A food composition for ameliorating and preventing glucagon hyperemia, which comprises alktigenin and / or alktiin as an active ingredient. A food composition containing necrolytic migratory erythema as an active ingredient, for improving and preventing necrolytic migratory erythema. The food composition according to any one of claims 5 to 7, which comprises the burdock, burdock, burdock sprout or forsythia or an extract thereof, which comprises the arktigenin and / or arktiin.

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