WO2016117654A1 - Early insulin secretion promoter - Google Patents
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- WO2016117654A1 WO2016117654A1 PCT/JP2016/051732 JP2016051732W WO2016117654A1 WO 2016117654 A1 WO2016117654 A1 WO 2016117654A1 JP 2016051732 W JP2016051732 W JP 2016051732W WO 2016117654 A1 WO2016117654 A1 WO 2016117654A1
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- insulin
- lactic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
Definitions
- the present invention relates to an agent for improving the initial secretory ability of insulin.
- Diabetes is a metabolic disease whose main feature is a hyperglycemic state.
- Chronic hyperglycemia persistence is known not only to cause microvascular disorders such as nephropathy, retinopathy and neuropathy, but also to promote the onset of arteriosclerotic diseases such as myocardial infarction and cerebral infarction. That is, it can be said that diabetes is a disease that greatly affects not only QOL but also life expectancy.
- type 2 diabetes has a relatively insufficient effect of insulin due to a decrease in insulin secretory ability of pancreatic ⁇ cells and a decrease in insulin sensitivity (insulin resistance) in target tissues such as liver, skeletal muscle, and fat. It becomes hyperglycemia by doing.
- Diabetes mellitus as a lifestyle-related disease that is rapidly increasing at present is type 2 diabetes, and Western lifestyles such as overeating, high-fat diet, and lack of exercise are strongly influenced as environmental factors.
- type 2 diabetes is mainly caused by a decrease in insulin secretion ability, particularly insulin secretion ability, which is necessary to suppress a rapid increase in blood glucose level after sugar intake, rather than insulin resistance. Therefore, a method for improving the initial secretory capacity is desired.
- Non-patent Document 1 the cell wall polysaccharide-glycan complex of Gram-positive bacteria suppresses the increase of blood glucose level and urine sugar (Patent Document 1) and the Lactobacillus casei cell body (dead cell body) It has been reported that it has an inhibitory effect on elevation (Non-patent Document 1).
- insulin secretagogues such as sulfonylurea drugs and glinide drugs are Not only early secretion (phase 1 additional secretion) but also late phase secretion (phase 2 additional secretion) and fasting basal secretion, in addition to the risk of hypoglycemia, causing fatigue of pancreatic ⁇ cells, There was a problem that the insulin secretion ability was further lowered and hyperglycemia was caused.
- an object of the present invention is to provide a new agent for improving early secretory ability of insulin.
- the present inventors have studied to solve the above-mentioned problems, and found that there is an action for improving the ability to secrete early insulin, which is specifically superior to viable bacteria, not dead lactic acid bacteria, and complete the present invention. It came to.
- the present invention provides the following [1] to [9].
- An insulin early secretory ability improving agent comprising a composition containing 1 ⁇ 10 10 cells or more of live lactic acid bacteria as an active ingredient.
- the early insulin secretion capacity improving agent according to any one of [1] to [3], wherein the lactic acid bacterium is Lactobacillus casei.
- a composition comprising 1 ⁇ 10 10 cells or more of live lactic acid bacteria for use in improving the initial secretory ability of insulin.
- a method for improving the initial secretory ability of insulin comprising administering or ingesting an effective amount of a composition containing 1 ⁇ 10 10 cells or more of live lactic acid bacteria to a subject in need thereof.
- the insulin early secretory capacity improving agent of the present invention has been found to have a particularly strong action of live bacteria of lactic acid bacteria. By improving only the initial secretory ability of insulin, the risk of hypoglycemia and further hyperglycemia induction due to exhaustion of pancreatic ⁇ cells is reduced.
- the active ingredient of the insulin early secretory ability improving agent of the present invention is a composition containing 1 ⁇ 10 10 cells or more of live lactic acid bacteria.
- lactic acid bacteria containing a large amount of dead bacteria did not have an effect of improving the initial secretion of insulin, and therefore the effects of the present invention are peculiar to live bacteria of lactic acid bacteria.
- the viable bacteria mentioned here are, for example, a composition appropriately diluted in physiological saline or Ringer's solution, applied to a medium suitable for measurement of lactic acid bacteria such as BCP-added plate count agar medium or mupirocin-added TOS propionic acid medium It can be measured by counting colonies of lactic acid bacteria that appeared after holding at 37 ° C. for 3 days. In the case of obligate anaerobic bacteria, it is sufficient to degas and hold in an anaerobic jar filled with carbon dioxide and / or nitrogen.
- Lactic acid bacteria are not particularly limited, and include Lactobacillus genus, Lactococcus genus, Enterococcus genus, Pediococcus genus, Leuconostoc genus, Bifidobacterium genus and the like. Among these, the genus Lactobacillus and the genus Bifidobacterium are preferable, and the genus Lactobacillus is more preferable.
- Lactobacillus lactic acid bacteria examples include Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus zeae, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus gasseri, etc. .
- Lactobacillus casei is preferable, and among Lactobacillus casei, Lactobacillus casei YIT9029 strain (FERM BP-1366) is more preferable.
- the insulin initial secretion index is the initial insulin calculated from the fasting blood glucose before fasting glucose and the fasting blood insulin, blood glucose 30 minutes after glucose loading and blood insulin in the 75 g oral glucose tolerance test by the following formula: The secretory index.
- the healthy human initial insulin secretion index is 0.4 or more, and the human initial insulin secretion index with abnormal insulin initial secretion ability is less than 0.4. It is said that humans with an initial insulin secretion index of less than 0.4 are likely to have diabetes.
- the improvement of the initial insulin secretion ability means that the insulin initial secretion index is set to a healthy human level, for example, the insulin initial secretion index is 0.4 or more, preferably 0.4 to 5.0. Means that. In addition, it means that the additional secretion of insulin in the second phase is not increased, preferably the blood insulin concentration 60 minutes after glucose loading or the blood insulin concentration 120 minutes after glucose loading is not increased. To do. *
- the subject who takes the agent for improving early insulin secretion ability of the present invention is not particularly limited, but is preferably a human having an early insulin secretion index of less than 0.4, that is, a type 2 diabetic patient or a type 2 diabetes preliminarily group. It is more preferable to target persons in the type 2 diabetes preparatory group.
- the type 2 diabetes preparatory group means a person with an initial insulin secretion index of less than 0.4 and a fasting blood glucose level of 100 mg / dL or more and / or a glucose load of 120 minutes or more and a glucose level of 130 mg / dL or more. A person who falls within the border between healthy and healthy people.
- the initial secretory ability improving agent for insulin of the present invention is preferably taken orally in 1 to 3 divided doses per day.
- the intake period is preferably taken continuously for 1 week or longer, more preferably taken continuously for 4 weeks or longer, particularly preferably taken continuously for 8 weeks or longer.
- the preparation of the insulin early secretory ability improving agent of the present invention is not limited as long as it is a composition containing 1 ⁇ 10 10 cells or more of live bacteria of lactic acid bacteria.
- it can be a conventional pharmaceutical preparation.
- preparations include solid agents such as tablets, granules, powders, and capsules, solutions such as solutions, suspensions, emulsions, freeze-dried agents, and the like. It can be prepared by mixing with a nontoxic pharmaceutical carrier as appropriate by conventional means.
- non-toxic pharmaceutical carriers include, for example, glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glycerides, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acids, gelatin, albumin , Water, physiological saline and the like.
- conventional additives such as stabilizers, wetting agents, emulsifiers, binders, isotonic agents, excipients and the like can be appropriately added as necessary.
- live bacteria of lactic acid bacteria in the form of a fermented product in terms of ease of intake, continuity of intake, and the like.
- fermented milk fermented soymilk, fermented fruit juice, fermented plant fluid, etc. fermented with lactic acid bacteria, which are active ingredients, are preferably used as fermented products.
- These fermented products can be produced according to a conventional method.
- fermented milk is obtained by inoculating and cultivating live lactic acid bacteria in a sterilized milk medium and homogenizing it to obtain a fermented milk base.
- a separately prepared syrup solution is added and mixed, homogenized with a homogenizer or the like, and flavor is further added to obtain a final product.
- Saccharomyces genus Candida genus, Rhodotorula genus, Pichia genus, Schizosaccharomyces genus, Torula genus, Tigosaccharomyces genus yeast, Aspergillus genus, Penicillium genus, Eurothium Fermentation such as genus, Monascus genus, Micol genus, Neurospora genus, and Rhizopus genus may be used in combination, but it is preferable to ferment only with lactic acid bacteria.
- Lactobacillus casei strain YIT9029 was inoculated, syrup was mixed with skim milk solution fermented at 37 ° C., flavor was added, homogenized and filled into a container to obtain the composition of the present invention. .
- the number of viable bacteria of Lactobacillus casei in 100 mL of this fermented dairy product was 1 ⁇ 10 11 cells.
- the composition which did not contain Lactobacillus casei and added the lactic acid equivalent to fermented dairy products and adjusted the flavor was used.
- about another composition it is the same as this invention composition.
- Test 1 (Example) (experimental method) 19 males with an initial insulin secretion index of less than 0.4 (the initial insulin secretion index, fasting blood glucose level, and average blood glucose level after 120 minutes of glucose loading were 0.28, 107 mg / dL, and 172 mg / dL, respectively) And 17 patients (average insulin initial secretion index, fasting blood glucose level, and blood glucose level after 120 minutes of glucose loading were 0.29, 111 mg / dL and 178 mg / dL, respectively).
- composition of the present invention A composition containing 1 ⁇ 10 11 cells of live casei (hereinafter referred to as “the composition of the present invention”) or a placebo containing no Lactobacillus casei was ingested once a day (100 mL) for 8 weeks.
- the subjects were instructed not to change their lifestyle, such as eating, drinking, sleeping, etc. as much as possible during the study, and to avoid excessive exercise, food saving, and overeating that greatly deviated from the normal range.
- Table 1 shows the initial secretion index of insulin before intake, 4 weeks, and 8 weeks. As shown in Table 1, it was confirmed that ingesting 1 ⁇ 10 11 cells per day of live Lactobacillus casei improved the initial insulin secretion compared with placebo. Although the results are not shown, in the group that ingested 1 ⁇ 10 11 cells per day of live Lactobacillus casei bacteria, there was almost no change in the fasting blood insulin concentration, which is an indicator of the basic secretory amount of insulin. There wasn't. Furthermore, the blood insulin concentration (Table 2) 60 minutes after loading 75 g glucose and the blood insulin concentration (Table 3) after 120 minutes, which are indicators of the amount of additional secretion in the second phase, are decreased.
- composition of the present invention does not increase the basal secretion of insulin and the additional secretion of the second phase. From this, it was confirmed that the initial secretory ability of insulin was specifically improved by ingesting 1 ⁇ 10 11 cells per day of live Lactobacillus casei.
- Test 2 (Comparative experiment) (experimental method) 8 males with an initial insulin secretion index of less than 0.4 (Insulin early secretion index, fasting blood glucose level, and average blood glucose level after 120 minutes of glucose load were 0.24, 117 mg / dL, and 173 mg / dL, respectively) And 7 people (Insulin initial secretion index, fasting blood glucose level, and average glucose level after 120 minutes of glucose loading are 0.16, 121 mg / dL and 189 mg / dL, respectively), Lactobacillus casei viable bacteria per 2 g 4 ⁇ 10 9 cells and 2 ⁇ 10 11 cells of dead bacteria, or a placebo containing no Lactobacillus casei was ingested once a day (2 g) for 8 weeks.
- Table 4 shows the initial secretory index of insulin before intake and after 8 weeks.
- the powder is prepared by adding a powder obtained by mixing skim milk powder and trehalose in a ratio of 2 to 1 to a freeze-dried powder containing live and dead bacteria of Lactobacillus casei YIT9029 strain to adjust the number of bacteria.
- a placebo is a mixture of skim milk powder and trehalose in a 2 to 1 ratio.
- the number of dead bacteria contained in the powder was determined by measuring the total number of Lactobacillus casei contained in the powder by the DAPI staining method and excluding the number of living bacteria therefrom.
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Abstract
Provided is an early insulin secretion promoter. An early insulin secretion promoter having as an active ingredient a composition containing 1 × 1010 cells or more of live lactic acid bacteria.
Description
本発明は、インスリン初期分泌能を改善する剤に関する。
The present invention relates to an agent for improving the initial secretory ability of insulin.
糖尿病は、高血糖状態を主徴とする代謝疾患である。慢性的な高血糖の持続は、腎症・網膜症・神経症といった細小血管障害を併発するだけでなく、心筋梗塞・脳梗塞といった動脈硬化性疾患の発症を促進することが知られている。すなわち、糖尿病は、ＱＯＬだけではなく余命をも大きく左右する疾患と言える。糖尿病には複数の病型が存在するが、主要な病型は１型糖尿病と２型糖尿病である。
Diabetes is a metabolic disease whose main feature is a hyperglycemic state. Chronic hyperglycemia persistence is known not only to cause microvascular disorders such as nephropathy, retinopathy and neuropathy, but also to promote the onset of arteriosclerotic diseases such as myocardial infarction and cerebral infarction. That is, it can be said that diabetes is a disease that greatly affects not only QOL but also life expectancy. There are several types of diabetes, but the main types are type 1 diabetes and type 2 diabetes.
このうち、２型糖尿病は、膵β細胞のインスリン分泌能の低下、ならびに、肝臓、骨格筋、脂肪などの標的組織におけるインスリン感受性の低下（インスリン抵抗性）により、インスリンの効果が相対的に不足することで高血糖となる。現在、急増している生活習慣病としての糖尿病は２型糖尿病であり、その発症には過食や高脂肪食、運動不足などの欧米型の生活習慣が環境因子として強く影響する。
また、日本人において２型糖尿病はインスリン抵抗性よりもインスリン分泌能、特に糖摂取後の急激な血糖値上昇を抑制するために必要なインスリン初期分泌能の低下が主因となる場合が多く、インスリンの初期分泌能を改善する方法が望まれている。 Among these, type 2 diabetes has a relatively insufficient effect of insulin due to a decrease in insulin secretory ability of pancreatic β cells and a decrease in insulin sensitivity (insulin resistance) in target tissues such as liver, skeletal muscle, and fat. It becomes hyperglycemia by doing. Diabetes mellitus as a lifestyle-related disease that is rapidly increasing at present is type 2 diabetes, and Western lifestyles such as overeating, high-fat diet, and lack of exercise are strongly influenced as environmental factors.
In Japanese, type 2 diabetes is mainly caused by a decrease in insulin secretion ability, particularly insulin secretion ability, which is necessary to suppress a rapid increase in blood glucose level after sugar intake, rather than insulin resistance. Therefore, a method for improving the initial secretory capacity is desired.
また、日本人において２型糖尿病はインスリン抵抗性よりもインスリン分泌能、特に糖摂取後の急激な血糖値上昇を抑制するために必要なインスリン初期分泌能の低下が主因となる場合が多く、インスリンの初期分泌能を改善する方法が望まれている。 Among these, type 2 diabetes has a relatively insufficient effect of insulin due to a decrease in insulin secretory ability of pancreatic β cells and a decrease in insulin sensitivity (insulin resistance) in target tissues such as liver, skeletal muscle, and fat. It becomes hyperglycemia by doing. Diabetes mellitus as a lifestyle-related disease that is rapidly increasing at present is type 2 diabetes, and Western lifestyles such as overeating, high-fat diet, and lack of exercise are strongly influenced as environmental factors.
In Japanese, type 2 diabetes is mainly caused by a decrease in insulin secretion ability, particularly insulin secretion ability, which is necessary to suppress a rapid increase in blood glucose level after sugar intake, rather than insulin resistance. Therefore, a method for improving the initial secretory capacity is desired.
一方、乳酸菌に関する報告として、グラム陽性菌の細胞壁の多糖－グリカン複合体が血糖値および尿糖の上昇を抑制すること（特許文献１）及びラクトバチルス・カゼイの菌体（死菌体）が血糖上昇抑制作用を有することが報告されている（非特許文献１）。
On the other hand, as a report on lactic acid bacteria, the cell wall polysaccharide-glycan complex of Gram-positive bacteria suppresses the increase of blood glucose level and urine sugar (Patent Document 1) and the Lactobacillus casei cell body (dead cell body) It has been reported that it has an inhibitory effect on elevation (Non-patent Document 1).
しかしながら、従来の血糖値低下剤は、空腹時の高血糖の改善に注目しすぎるあまり低血糖を引き起こすリスクがあり、なかでもスルホニル尿素薬やグリニド薬をはじめとするインスリン分泌促進剤は、食後の初期分泌（第１相の追加分泌）だけではなく、後期分泌（第２相の追加分泌）や空腹時の基礎分泌を高めてしまうため、低血糖リスクに加え、膵β細胞の疲弊を引き起こし、更なるインスリン分泌能の低下と高血糖をもたらすという問題があった。このような問題を解決するため、また上述の通り、日本人の２型糖尿病はインスリン初期分泌能の低下が主因となることから、初期分泌能のみを改善する剤の開発が望まれている。
従って、本発明の課題は、新たなインスリン初期分泌能改善剤を提供することにある。 However, conventional blood glucose level lowering agents have a risk of causing hypoglycemia that is too focused on improving fasting hyperglycemia. Among them, insulin secretagogues such as sulfonylurea drugs and glinide drugs are Not only early secretion (phase 1 additional secretion) but also late phase secretion (phase 2 additional secretion) and fasting basal secretion, in addition to the risk of hypoglycemia, causing fatigue of pancreatic β cells, There was a problem that the insulin secretion ability was further lowered and hyperglycemia was caused. In order to solve such problems and as described above, Japanese type 2 diabetes is mainly caused by a decrease in the initial secretory ability, and therefore development of an agent that improves only the initial secretory ability is desired.
Accordingly, an object of the present invention is to provide a new agent for improving early secretory ability of insulin.
従って、本発明の課題は、新たなインスリン初期分泌能改善剤を提供することにある。 However, conventional blood glucose level lowering agents have a risk of causing hypoglycemia that is too focused on improving fasting hyperglycemia. Among them, insulin secretagogues such as sulfonylurea drugs and glinide drugs are Not only early secretion (phase 1 additional secretion) but also late phase secretion (phase 2 additional secretion) and fasting basal secretion, in addition to the risk of hypoglycemia, causing fatigue of pancreatic β cells, There was a problem that the insulin secretion ability was further lowered and hyperglycemia was caused. In order to solve such problems and as described above, Japanese type 2 diabetes is mainly caused by a decrease in the initial secretory ability, and therefore development of an agent that improves only the initial secretory ability is desired.
Accordingly, an object of the present invention is to provide a new agent for improving early secretory ability of insulin.
そこで本発明者は、前記課題を解決すべく検討してきたところ、乳酸菌の死菌体でなく、生菌に特異的に優れたインスリン初期分泌能改善作用があることを見出し、本発明を完成するに至った。
Thus, the present inventors have studied to solve the above-mentioned problems, and found that there is an action for improving the ability to secrete early insulin, which is specifically superior to viable bacteria, not dead lactic acid bacteria, and complete the present invention. It came to.
すなわち、本発明は、次の〔１〕～〔９〕を提供するものである。
That is, the present invention provides the following [1] to [9].
〔１〕乳酸菌の生菌を１×１０10cells以上含む組成物を有効成分とするインスリン初期分泌能改善剤。
〔２〕乳酸菌の生菌を１日あたり１×１０10cells以上摂取する〔１〕記載のインスリン初期分泌能改善剤。
〔３〕乳酸菌が、ラクトバチルス属に属する乳酸菌である〔１〕又は〔２〕記載のインスリン初期分泌能改善剤。
〔４〕乳酸菌が、ラクトバチルス・カゼイである〔１〕～〔３〕のいずれかに記載のインスリン初期分泌能改善剤。
〔５〕乳酸菌が、ラクトバチルス・カゼイ ＹＩＴ９０２９株である〔１〕～〔４〕のいずれかに記載のインスリン初期分泌能改善剤。
〔６〕インスリン初期分泌能改善剤を製造するための、乳酸菌の生菌を１×１０10cells以上含む組成物の使用。
〔７〕インスリン初期分泌能改善に使用するための、乳酸菌の生菌を１×１０10cells以上含む組成物。
〔８〕乳酸菌の生菌を１×１０10cells以上含む組成物を、それらを必要とする対象に有効量で投与又は摂取するインスリン初期分泌能改善方法。
〔９〕乳酸菌の生菌を１日あたり１×１０10cells以上摂取する、〔８〕記載のインスリン初期分泌能改善方法。 [1] An insulin early secretory ability improving agent comprising a composition containing 1 × 10 10 cells or more of live lactic acid bacteria as an active ingredient.
[2] The insulin early secretory capacity improving agent according to [1], wherein 1 × 10 10 cells or more of live lactic acid bacteria are ingested per day.
[3] The insulin initial secretory ability improving agent according to [1] or [2], wherein the lactic acid bacterium is a lactic acid bacterium belonging to the genus Lactobacillus.
[4] The early insulin secretion capacity improving agent according to any one of [1] to [3], wherein the lactic acid bacterium is Lactobacillus casei.
[5] The insulin early secretory ability improving agent according to any one of [1] to [4], wherein the lactic acid bacterium is Lactobacillus casei YIT9029 strain.
[6] Use of a composition containing 1 × 10 10 cells or more of live lactic acid bacteria for producing an agent for improving early secretory ability of insulin.
[7] A composition comprising 1 × 10 10 cells or more of live lactic acid bacteria for use in improving the initial secretory ability of insulin.
[8] A method for improving the initial secretory ability of insulin, comprising administering or ingesting an effective amount of a composition containing 1 × 10 10 cells or more of live lactic acid bacteria to a subject in need thereof.
[9] The method for improving the initial secretory ability of insulin according to [8], wherein 1 × 10 10 cells or more of lactic acid bacteria are ingested per day.
〔２〕乳酸菌の生菌を１日あたり１×１０10cells以上摂取する〔１〕記載のインスリン初期分泌能改善剤。
〔３〕乳酸菌が、ラクトバチルス属に属する乳酸菌である〔１〕又は〔２〕記載のインスリン初期分泌能改善剤。
〔４〕乳酸菌が、ラクトバチルス・カゼイである〔１〕～〔３〕のいずれかに記載のインスリン初期分泌能改善剤。
〔５〕乳酸菌が、ラクトバチルス・カゼイ ＹＩＴ９０２９株である〔１〕～〔４〕のいずれかに記載のインスリン初期分泌能改善剤。
〔６〕インスリン初期分泌能改善剤を製造するための、乳酸菌の生菌を１×１０10cells以上含む組成物の使用。
〔７〕インスリン初期分泌能改善に使用するための、乳酸菌の生菌を１×１０10cells以上含む組成物。
〔８〕乳酸菌の生菌を１×１０10cells以上含む組成物を、それらを必要とする対象に有効量で投与又は摂取するインスリン初期分泌能改善方法。
〔９〕乳酸菌の生菌を１日あたり１×１０10cells以上摂取する、〔８〕記載のインスリン初期分泌能改善方法。 [1] An insulin early secretory ability improving agent comprising a composition containing 1 × 10 10 cells or more of live lactic acid bacteria as an active ingredient.
[2] The insulin early secretory capacity improving agent according to [1], wherein 1 × 10 10 cells or more of live lactic acid bacteria are ingested per day.
[3] The insulin initial secretory ability improving agent according to [1] or [2], wherein the lactic acid bacterium is a lactic acid bacterium belonging to the genus Lactobacillus.
[4] The early insulin secretion capacity improving agent according to any one of [1] to [3], wherein the lactic acid bacterium is Lactobacillus casei.
[5] The insulin early secretory ability improving agent according to any one of [1] to [4], wherein the lactic acid bacterium is Lactobacillus casei YIT9029 strain.
[6] Use of a composition containing 1 × 10 10 cells or more of live lactic acid bacteria for producing an agent for improving early secretory ability of insulin.
[7] A composition comprising 1 × 10 10 cells or more of live lactic acid bacteria for use in improving the initial secretory ability of insulin.
[8] A method for improving the initial secretory ability of insulin, comprising administering or ingesting an effective amount of a composition containing 1 × 10 10 cells or more of live lactic acid bacteria to a subject in need thereof.
[9] The method for improving the initial secretory ability of insulin according to [8], wherein 1 × 10 10 cells or more of lactic acid bacteria are ingested per day.
本発明のインスリン初期分泌能改善剤は、乳酸菌の生菌が特に強い作用を有することを見出したものである。インスリンの初期分泌能のみを改善することで、低血糖リスクや膵β細胞の疲弊による更なる高血糖誘発の危険性が少ない。
The insulin early secretory capacity improving agent of the present invention has been found to have a particularly strong action of live bacteria of lactic acid bacteria. By improving only the initial secretory ability of insulin, the risk of hypoglycemia and further hyperglycemia induction due to exhaustion of pancreatic β cells is reduced.
本発明のインスリン初期分泌能改善剤の有効成分は、乳酸菌の生菌を１×１０10cells以上含む組成物である。後記実施例に示すように、死菌を多量に含む乳酸菌では、インスリン初期分泌の改善効果がなかったことから、本発明の効果は、乳酸菌の生菌特有のものである。ここで言うところの生菌は、例えば、生理食塩水またはリンゲル液に適宜希釈した組成物を、ＢＣＰ加プレートカウント寒天培地またはムピロシン加ＴＯＳプロピオン酸培地等の乳酸菌の測定に適した培地に塗布し、３７℃、３日間保持した後に出現した乳酸菌のコロニーをカウントすることにより測定することができる。なお、偏性嫌気性菌の場合は脱気して二酸化炭素および/または窒素を充填した嫌気ジャーにいれて保持すればよい。
The active ingredient of the insulin early secretory ability improving agent of the present invention is a composition containing 1 × 10 10 cells or more of live lactic acid bacteria. As shown in Examples below, lactic acid bacteria containing a large amount of dead bacteria did not have an effect of improving the initial secretion of insulin, and therefore the effects of the present invention are peculiar to live bacteria of lactic acid bacteria. The viable bacteria mentioned here are, for example, a composition appropriately diluted in physiological saline or Ringer's solution, applied to a medium suitable for measurement of lactic acid bacteria such as BCP-added plate count agar medium or mupirocin-added TOS propionic acid medium It can be measured by counting colonies of lactic acid bacteria that appeared after holding at 37 ° C. for 3 days. In the case of obligate anaerobic bacteria, it is sufficient to degas and hold in an anaerobic jar filled with carbon dioxide and / or nitrogen.
乳酸菌としては、特に限定されず、ラクトバチルス属、ラクトコッカス属、エンテロコッカス属、ペディオコッカス属、リューコノストック属、ビフィドバクテリウム属等が挙げられる。このうち、ラクトバチルス属、ビフィドバクテリウム属が好ましく、ラクトバチルス属がより好ましい。
さらに、ラクトバチルス属の乳酸菌としては、ラクトバチルス・カゼイ、ラクトバチルス・ラムノーサス、ラクトバチルス・ゼアエ、ラクトバチルス・ブルガリカス、ラクトバチルス・アシドフィルス、ラクトバチルス・プランタラム、ラクトバチルス・ガッセリ等が挙げられる。このうち、ラクトバチルス・カゼイが好ましく、ラクトバチルス・カゼイの中でもラクトバチルス・カゼイ ＹＩＴ９０２９株（ＦＥＲＭ ＢＰ－１３６６）がさらに好ましい。 Lactic acid bacteria are not particularly limited, and include Lactobacillus genus, Lactococcus genus, Enterococcus genus, Pediococcus genus, Leuconostoc genus, Bifidobacterium genus and the like. Among these, the genus Lactobacillus and the genus Bifidobacterium are preferable, and the genus Lactobacillus is more preferable.
Furthermore, examples of Lactobacillus lactic acid bacteria include Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus zeae, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus gasseri, etc. . Among these, Lactobacillus casei is preferable, and among Lactobacillus casei, Lactobacillus casei YIT9029 strain (FERM BP-1366) is more preferable.
さらに、ラクトバチルス属の乳酸菌としては、ラクトバチルス・カゼイ、ラクトバチルス・ラムノーサス、ラクトバチルス・ゼアエ、ラクトバチルス・ブルガリカス、ラクトバチルス・アシドフィルス、ラクトバチルス・プランタラム、ラクトバチルス・ガッセリ等が挙げられる。このうち、ラクトバチルス・カゼイが好ましく、ラクトバチルス・カゼイの中でもラクトバチルス・カゼイ ＹＩＴ９０２９株（ＦＥＲＭ ＢＰ－１３６６）がさらに好ましい。 Lactic acid bacteria are not particularly limited, and include Lactobacillus genus, Lactococcus genus, Enterococcus genus, Pediococcus genus, Leuconostoc genus, Bifidobacterium genus and the like. Among these, the genus Lactobacillus and the genus Bifidobacterium are preferable, and the genus Lactobacillus is more preferable.
Furthermore, examples of Lactobacillus lactic acid bacteria include Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus zeae, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus gasseri, etc. . Among these, Lactobacillus casei is preferable, and among Lactobacillus casei, Lactobacillus casei YIT9029 strain (FERM BP-1366) is more preferable.
乳酸菌の生菌は、後記実施例に示すように、インスリン初期分泌指数を改善する効果を有する。ここで、インスリン初期分泌指数とは、７５ｇ経口ブドウ糖負荷試験でブドウ糖負荷前の空腹時血糖と空腹時血中インスリン、ブドウ糖負荷後３０分の血糖と血中インスリンから次式で計算されるインスリン初期分泌指数をいう。
Live bacteria of lactic acid bacteria have the effect of improving the initial insulin secretion index, as shown in the Examples below. Here, the insulin initial secretion index is the initial insulin calculated from the fasting blood glucose before fasting glucose and the fasting blood insulin, blood glucose 30 minutes after glucose loading and blood insulin in the 75 g oral glucose tolerance test by the following formula: The secretory index.
健康なヒトのインスリン初期分泌指数は０．４以上であり、インスリン初期分泌能に異常のあるヒトのインスリン初期分泌指数は０．４未満である。インスリン初期分泌指数が０．４未満のヒトは糖尿病になる可能性が高いといわれている。
The healthy human initial insulin secretion index is 0.4 or more, and the human initial insulin secretion index with abnormal insulin initial secretion ability is less than 0.4. It is said that humans with an initial insulin secretion index of less than 0.4 are likely to have diabetes.
本発明において、インスリン初期分泌能改善とは、斯かるインスリン初期分泌指数を健康なヒトのレベルにすること、例えばインスリン初期分泌指数を０．４以上、好ましくは０．４～５．０にすることを意味する。また、併せて第２相のインスリンの追加分泌を増加させないこと、好ましくは、ブドウ糖負荷後６０分後の血中インスリン濃度、或いはブドウ糖負荷後１２０分後の血中インスリン濃度を増加させないことを意味する。
In the present invention, the improvement of the initial insulin secretion ability means that the insulin initial secretion index is set to a healthy human level, for example, the insulin initial secretion index is 0.4 or more, preferably 0.4 to 5.0. Means that. In addition, it means that the additional secretion of insulin in the second phase is not increased, preferably the blood insulin concentration 60 minutes after glucose loading or the blood insulin concentration 120 minutes after glucose loading is not increased. To do. *
インスリン初期分泌指数が０．４未満のヒトに１日あたり乳酸菌１×１０11cellsを摂取させたところ、インスリン初期分泌指数が改善された。一方、乳酸菌の生菌の摂取量が少ない場合には、インスリン初期分泌指数の改善効果は得られなかった。
従って、乳酸菌の生菌を１日あたり１×１０10cells以上含む組成物を摂取するのが好ましく、乳酸菌の生菌を１日あたり１×１０11cells以上含む組成物を摂取するのがより好ましく、乳酸菌の生菌を１日あたり１×１０11cells～１×１０12cells含む組成物を摂取するのがさらに好ましい。 When a human having an initial insulin secretion index of less than 0.4 was ingested with 1 × 10 11 cells of lactic acid bacteria per day, the insulin initial secretion index was improved. On the other hand, when the intake of live lactic acid bacteria was small, the effect of improving the initial insulin secretion index could not be obtained.
Therefore, it is preferable to ingest a composition containing 1 × 10 10 cells or more of live lactic acid bacteria per day, and more preferably to ingest a composition containing 1 × 10 11 cells or more of live lactic acid bacteria per day. It is more preferable to take a composition containing 1 × 10 11 cells to 1 × 10 12 cells of lactic acid bacteria per day.
従って、乳酸菌の生菌を１日あたり１×１０10cells以上含む組成物を摂取するのが好ましく、乳酸菌の生菌を１日あたり１×１０11cells以上含む組成物を摂取するのがより好ましく、乳酸菌の生菌を１日あたり１×１０11cells～１×１０12cells含む組成物を摂取するのがさらに好ましい。 When a human having an initial insulin secretion index of less than 0.4 was ingested with 1 × 10 11 cells of lactic acid bacteria per day, the insulin initial secretion index was improved. On the other hand, when the intake of live lactic acid bacteria was small, the effect of improving the initial insulin secretion index could not be obtained.
Therefore, it is preferable to ingest a composition containing 1 × 10 10 cells or more of live lactic acid bacteria per day, and more preferably to ingest a composition containing 1 × 10 11 cells or more of live lactic acid bacteria per day. It is more preferable to take a composition containing 1 × 10 11 cells to 1 × 10 12 cells of lactic acid bacteria per day.
本発明のインスリン初期分泌能改善剤の摂取対象者は特に限定されないが、インスリン初期分泌指数が０．４未満のヒト、すなわち、２型糖尿病患者又は２型糖尿病予備群の者が好ましく、特に２型糖尿病予備群の者を対象とすることがより好ましい。ここで２型糖尿病予備群とは、インスリン初期分泌指数が０．４未満でかつ、空腹時血糖値１００mg／dL以上及び／又はブドウ糖負荷１２０分血糖値１３０mg／dL以上の者をいい、糖尿病患者と健常者の境界域に該当する者をさす。
The subject who takes the agent for improving early insulin secretion ability of the present invention is not particularly limited, but is preferably a human having an early insulin secretion index of less than 0.4, that is, a type 2 diabetic patient or a type 2 diabetes preliminarily group. It is more preferable to target persons in the type 2 diabetes preparatory group. Here, the type 2 diabetes preparatory group means a person with an initial insulin secretion index of less than 0.4 and a fasting blood glucose level of 100 mg / dL or more and / or a glucose load of 120 minutes or more and a glucose level of 130 mg / dL or more. A person who falls within the border between healthy and healthy people.
本発明のインスリン初期分泌能改善剤は、１日あたり１～３回に分けて経口的に摂取するのが好ましい。また、摂取期間としては１週間以上連続して摂取することが好ましく、４週間以上連続で摂取することが更に好ましく、８週間以上連続して摂取するのが特に好ましい。
The initial secretory ability improving agent for insulin of the present invention is preferably taken orally in 1 to 3 divided doses per day. The intake period is preferably taken continuously for 1 week or longer, more preferably taken continuously for 4 weeks or longer, particularly preferably taken continuously for 8 weeks or longer.
本発明のインスリン初期分泌能改善剤は、乳酸菌の生菌を１×１０10cells以上含む組成物であればその製剤形態は限定されず、例えば、慣用の医薬品製剤とすることができる。このような製剤としては、例えば、錠剤、顆粒剤、散剤、カプセル剤等の固体剤、溶液剤、懸濁剤、乳剤等の液剤、凍結乾燥剤等が挙げられ、これらの製剤は製剤上の常套手段により、適宜医薬用無毒性担体と混合することにより調製することができる。斯かる医薬用無毒性担体としては、例えば、グルコース、乳糖、ショ糖、澱粉、マンニトール、デキストリン、脂肪酸グリセリド、ポリエチレングリコール、ヒドロキシエチルデンプン、エチレングリコール、ポリオキシエチレンソルビタン脂肪酸エステル、アミノ酸、ゼラチン、アルブミン、水、生理食塩水等が挙げられる。また、必要に応じて、安定化剤、湿潤剤、乳化剤、結合剤、等張化剤、賦形剤等の慣用の添加剤を適宜添加することもできる。
The preparation of the insulin early secretory ability improving agent of the present invention is not limited as long as it is a composition containing 1 × 10 10 cells or more of live bacteria of lactic acid bacteria. For example, it can be a conventional pharmaceutical preparation. Examples of such preparations include solid agents such as tablets, granules, powders, and capsules, solutions such as solutions, suspensions, emulsions, freeze-dried agents, and the like. It can be prepared by mixing with a nontoxic pharmaceutical carrier as appropriate by conventional means. Such non-toxic pharmaceutical carriers include, for example, glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glycerides, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acids, gelatin, albumin , Water, physiological saline and the like. In addition, conventional additives such as stabilizers, wetting agents, emulsifiers, binders, isotonic agents, excipients and the like can be appropriately added as necessary.
また、乳酸菌の生菌は、摂取の容易性、摂取の継続性等の点から、発酵物の形態で用いるのが好ましい。
In addition, it is preferable to use live bacteria of lactic acid bacteria in the form of a fermented product in terms of ease of intake, continuity of intake, and the like.
ここで、発酵物としては、有効成分である乳酸菌生菌によって発酵させた発酵乳、発酵豆乳、発酵果汁、発酵植物液等が好適に用いられる。これら発酵物の製造は定法に従って製造することができる。例えば発酵乳は、殺菌した乳培地に乳酸菌生菌を接種培養し、これを均質化処理して発酵乳ベースを得る。この時、次いで別途調製したシロップ溶液を添加混合し、ホモゲナイザー等で均質化し、更にフレーバーを添加して最終製品とすることができる。
Here, fermented milk, fermented soymilk, fermented fruit juice, fermented plant fluid, etc. fermented with lactic acid bacteria, which are active ingredients, are preferably used as fermented products. These fermented products can be produced according to a conventional method. For example, fermented milk is obtained by inoculating and cultivating live lactic acid bacteria in a sterilized milk medium and homogenizing it to obtain a fermented milk base. At this time, a separately prepared syrup solution is added and mixed, homogenized with a homogenizer or the like, and flavor is further added to obtain a final product.
また、培養にあたっては、乳酸菌に他の微生物、例えば、サッカロミセス属、キャンディダ属、ロドトルーラ属、ピチア属、シゾサッカロミセス属、トルラ属、チゴサッカロミセス属等の酵母類、アスペルギルス属、ペニシリウム属、ユウロチウム属、モナスカス属、ミコール属、ニュウロスポラ属、リゾープス属等の糸状菌等を併用して発酵を行っても良いが、乳酸菌のみで発酵することが好ましい。
In culturing, other microorganisms such as Saccharomyces genus, Candida genus, Rhodotorula genus, Pichia genus, Schizosaccharomyces genus, Torula genus, Tigosaccharomyces genus yeast, Aspergillus genus, Penicillium genus, Eurothium Fermentation such as genus, Monascus genus, Micol genus, Neurospora genus, and Rhizopus genus may be used in combination, but it is preferable to ferment only with lactic acid bacteria.
次に実施例を挙げて本発明を更に詳細に説明する。
Next, the present invention will be described in more detail with reference to examples.
製造例１（本発明組成物の製造）
ラクトバチルス・カゼイ（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｃａｓｅｉ）ＹＩＴ９０２９株を接種し、３７℃で発酵させた脱脂粉乳溶液にシロップを混合し、香料を添加した後、均質化して容器に充填して本発明組成物を得た。この発酵乳製品１００ｍＬ中のラクトバチルス・カゼイの生菌数は１×１０11cellsであった。
また、プラセボとして、ラクトバチルス・カゼイを含まず、発酵乳製品と同等の乳酸を添加して風味を調整した組成物を用いた。なお、その他の組成については、本発明組成物と同じである。 Production Example 1 (Production of the composition of the present invention)
Lactobacillus casei strain YIT9029 was inoculated, syrup was mixed with skim milk solution fermented at 37 ° C., flavor was added, homogenized and filled into a container to obtain the composition of the present invention. . The number of viable bacteria of Lactobacillus casei in 100 mL of this fermented dairy product was 1 × 10 11 cells.
Moreover, as a placebo, the composition which did not contain Lactobacillus casei and added the lactic acid equivalent to fermented dairy products and adjusted the flavor was used. In addition, about another composition, it is the same as this invention composition.
ラクトバチルス・カゼイ（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｃａｓｅｉ）ＹＩＴ９０２９株を接種し、３７℃で発酵させた脱脂粉乳溶液にシロップを混合し、香料を添加した後、均質化して容器に充填して本発明組成物を得た。この発酵乳製品１００ｍＬ中のラクトバチルス・カゼイの生菌数は１×１０11cellsであった。
また、プラセボとして、ラクトバチルス・カゼイを含まず、発酵乳製品と同等の乳酸を添加して風味を調整した組成物を用いた。なお、その他の組成については、本発明組成物と同じである。 Production Example 1 (Production of the composition of the present invention)
Lactobacillus casei strain YIT9029 was inoculated, syrup was mixed with skim milk solution fermented at 37 ° C., flavor was added, homogenized and filled into a container to obtain the composition of the present invention. . The number of viable bacteria of Lactobacillus casei in 100 mL of this fermented dairy product was 1 × 10 11 cells.
Moreover, as a placebo, the composition which did not contain Lactobacillus casei and added the lactic acid equivalent to fermented dairy products and adjusted the flavor was used. In addition, about another composition, it is the same as this invention composition.
試験１（実施例）
（実験方法）
インスリン初期分泌指数が０．４未満の男性、１９名（インスリン初期分泌指数、空腹時血糖値、ブドウ糖負荷１２０分後血糖値の平均値は、それぞれ０．２８、１０７mg/dLおよび１７２mg/dL）および１７名（インスリン初期分泌指数、空腹時血糖値、ブドウ糖負荷１２０分後血糖値の平均値は、それぞれ０．２９、１１１mg/dLおよび１７８mg/dL）に対し、それぞれ製造例１のラクトバチルス・カゼイ生菌を１×１０11cells含む組成物（以下、本発明組成物という）、または、ラクトバチルス・カゼイを含まないプラセボを１日１本（１００ｍＬ）ずつ８週間摂取させた。なお、被験者に対し、試験中は試験参加前の食事、飲酒、睡眠等の生活習慣を極力変えないこと、通常範囲を大きく逸脱する過度な運動、節食、過食を避けることを指示した。 Test 1 (Example)
(experimental method)
19 males with an initial insulin secretion index of less than 0.4 (the initial insulin secretion index, fasting blood glucose level, and average blood glucose level after 120 minutes of glucose loading were 0.28, 107 mg / dL, and 172 mg / dL, respectively) And 17 patients (average insulin initial secretion index, fasting blood glucose level, and blood glucose level after 120 minutes of glucose loading were 0.29, 111 mg / dL and 178 mg / dL, respectively). A composition containing 1 × 10 11 cells of live casei (hereinafter referred to as “the composition of the present invention”) or a placebo containing no Lactobacillus casei was ingested once a day (100 mL) for 8 weeks. During the study, the subjects were instructed not to change their lifestyle, such as eating, drinking, sleeping, etc. as much as possible during the study, and to avoid excessive exercise, food saving, and overeating that greatly deviated from the normal range.
（実験方法）
インスリン初期分泌指数が０．４未満の男性、１９名（インスリン初期分泌指数、空腹時血糖値、ブドウ糖負荷１２０分後血糖値の平均値は、それぞれ０．２８、１０７mg/dLおよび１７２mg/dL）および１７名（インスリン初期分泌指数、空腹時血糖値、ブドウ糖負荷１２０分後血糖値の平均値は、それぞれ０．２９、１１１mg/dLおよび１７８mg/dL）に対し、それぞれ製造例１のラクトバチルス・カゼイ生菌を１×１０11cells含む組成物（以下、本発明組成物という）、または、ラクトバチルス・カゼイを含まないプラセボを１日１本（１００ｍＬ）ずつ８週間摂取させた。なお、被験者に対し、試験中は試験参加前の食事、飲酒、睡眠等の生活習慣を極力変えないこと、通常範囲を大きく逸脱する過度な運動、節食、過食を避けることを指示した。 Test 1 (Example)
(experimental method)
19 males with an initial insulin secretion index of less than 0.4 (the initial insulin secretion index, fasting blood glucose level, and average blood glucose level after 120 minutes of glucose loading were 0.28, 107 mg / dL, and 172 mg / dL, respectively) And 17 patients (average insulin initial secretion index, fasting blood glucose level, and blood glucose level after 120 minutes of glucose loading were 0.29, 111 mg / dL and 178 mg / dL, respectively). A composition containing 1 × 10 11 cells of live casei (hereinafter referred to as “the composition of the present invention”) or a placebo containing no Lactobacillus casei was ingested once a day (100 mL) for 8 weeks. During the study, the subjects were instructed not to change their lifestyle, such as eating, drinking, sleeping, etc. as much as possible during the study, and to avoid excessive exercise, food saving, and overeating that greatly deviated from the normal range.
（結果）
摂取前、４週間後、８週間後のインスリン初期分泌指数を表１に示す。表１に示すように、ラクトバチルス・カゼイ生菌を１日あたり１×１０11cells摂取することにより、プラセボと比較して、インスリン初期分泌が改善することが確認された。また、結果は示していないが、ラクトバチルス・カゼイ生菌を１日あたり１×１０11cellsを摂取した群では、インスリンの基礎分泌量の指標である空腹時血中インスリン濃度にはほとんど変化がなかった。更に、第２相の追加分泌量の指標である、７５ｇブドウ糖負荷後６０分後の血中インスリン濃度（表２）および１２０分後の血中インスリン濃度（表３）は減少していることから、本発明組成物は、インスリンの基礎分泌と第２相の追加分泌は増加させないことが確認された。このことから、ラクトバチルス・カゼイ生菌を１日あたり１×１０11cells摂取することにより、インスリンの初期分泌能を特異的に改善することが確認された。 (result)
Table 1 shows the initial secretion index of insulin before intake, 4 weeks, and 8 weeks. As shown in Table 1, it was confirmed that ingesting 1 × 10 11 cells per day of live Lactobacillus casei improved the initial insulin secretion compared with placebo. Although the results are not shown, in the group that ingested 1 × 10 11 cells per day of live Lactobacillus casei bacteria, there was almost no change in the fasting blood insulin concentration, which is an indicator of the basic secretory amount of insulin. There wasn't. Furthermore, the blood insulin concentration (Table 2) 60 minutes after loading 75 g glucose and the blood insulin concentration (Table 3) after 120 minutes, which are indicators of the amount of additional secretion in the second phase, are decreased. It was confirmed that the composition of the present invention does not increase the basal secretion of insulin and the additional secretion of the second phase. From this, it was confirmed that the initial secretory ability of insulin was specifically improved by ingesting 1 × 10 11 cells per day of live Lactobacillus casei.
摂取前、４週間後、８週間後のインスリン初期分泌指数を表１に示す。表１に示すように、ラクトバチルス・カゼイ生菌を１日あたり１×１０11cells摂取することにより、プラセボと比較して、インスリン初期分泌が改善することが確認された。また、結果は示していないが、ラクトバチルス・カゼイ生菌を１日あたり１×１０11cellsを摂取した群では、インスリンの基礎分泌量の指標である空腹時血中インスリン濃度にはほとんど変化がなかった。更に、第２相の追加分泌量の指標である、７５ｇブドウ糖負荷後６０分後の血中インスリン濃度（表２）および１２０分後の血中インスリン濃度（表３）は減少していることから、本発明組成物は、インスリンの基礎分泌と第２相の追加分泌は増加させないことが確認された。このことから、ラクトバチルス・カゼイ生菌を１日あたり１×１０11cells摂取することにより、インスリンの初期分泌能を特異的に改善することが確認された。 (result)
Table 1 shows the initial secretion index of insulin before intake, 4 weeks, and 8 weeks. As shown in Table 1, it was confirmed that ingesting 1 × 10 11 cells per day of live Lactobacillus casei improved the initial insulin secretion compared with placebo. Although the results are not shown, in the group that ingested 1 × 10 11 cells per day of live Lactobacillus casei bacteria, there was almost no change in the fasting blood insulin concentration, which is an indicator of the basic secretory amount of insulin. There wasn't. Furthermore, the blood insulin concentration (Table 2) 60 minutes after loading 75 g glucose and the blood insulin concentration (Table 3) after 120 minutes, which are indicators of the amount of additional secretion in the second phase, are decreased. It was confirmed that the composition of the present invention does not increase the basal secretion of insulin and the additional secretion of the second phase. From this, it was confirmed that the initial secretory ability of insulin was specifically improved by ingesting 1 × 10 11 cells per day of live Lactobacillus casei.
試験２（比較実験）
（実験方法）
インスリン初期分泌指数が０．４未満の男性、８名（インスリン初期分泌指数、空腹時血糖値、ブドウ糖負荷１２０分後血糖値の平均値は、それぞれ０．２４、１１７mg/dLおよび１７３mg/dL）および７名（インスリン初期分泌指数、空腹時血糖値、ブドウ糖負荷１２０分後血糖値の平均値は、それぞれ０．１６、１２１mg/dLおよび１８９mg/dL）に対し、２ｇあたりラクトバチルス・カゼイ生菌を４×１０9cellsおよび死菌を２×１０11cells、含む粉末、または、ラクトバチルス・カゼイを含まないプラセボをそれぞれ１日１包（２ｇ）ずつ８週間摂取させた。摂取前、８週間後のインスリン初期分泌指数を表４に示す。なお、粉末とは、ラクトバチルス・カゼイＹＩＴ９０２９株の生菌および死菌を含む凍結乾燥粉末に対し、脱脂粉乳とトレハロースを２対１で混合した粉末を加えて上記菌数に調整したものであり、プラセボとは脱脂粉乳とトレハロースを２対１で混合したものである。なお、粉末に含まれる死菌数は、ＤＡＰＩ染色法よって粉末に含まれるラクトバチルス・カゼイの総菌数を測定し、そこから生菌数を除くことで求めた。 Test 2 (Comparative experiment)
(experimental method)
8 males with an initial insulin secretion index of less than 0.4 (Insulin early secretion index, fasting blood glucose level, and average blood glucose level after 120 minutes of glucose load were 0.24, 117 mg / dL, and 173 mg / dL, respectively) And 7 people (Insulin initial secretion index, fasting blood glucose level, and average glucose level after 120 minutes of glucose loading are 0.16, 121 mg / dL and 189 mg / dL, respectively), Lactobacillus casei viable bacteria per 2 g 4 × 10 9 cells and 2 × 10 11 cells of dead bacteria, or a placebo containing no Lactobacillus casei was ingested once a day (2 g) for 8 weeks. Table 4 shows the initial secretory index of insulin before intake and after 8 weeks. The powder is prepared by adding a powder obtained by mixing skim milk powder and trehalose in a ratio of 2 to 1 to a freeze-dried powder containing live and dead bacteria of Lactobacillus casei YIT9029 strain to adjust the number of bacteria. A placebo is a mixture of skim milk powder and trehalose in a 2 to 1 ratio. The number of dead bacteria contained in the powder was determined by measuring the total number of Lactobacillus casei contained in the powder by the DAPI staining method and excluding the number of living bacteria therefrom.
（実験方法）
インスリン初期分泌指数が０．４未満の男性、８名（インスリン初期分泌指数、空腹時血糖値、ブドウ糖負荷１２０分後血糖値の平均値は、それぞれ０．２４、１１７mg/dLおよび１７３mg/dL）および７名（インスリン初期分泌指数、空腹時血糖値、ブドウ糖負荷１２０分後血糖値の平均値は、それぞれ０．１６、１２１mg/dLおよび１８９mg/dL）に対し、２ｇあたりラクトバチルス・カゼイ生菌を４×１０9cellsおよび死菌を２×１０11cells、含む粉末、または、ラクトバチルス・カゼイを含まないプラセボをそれぞれ１日１包（２ｇ）ずつ８週間摂取させた。摂取前、８週間後のインスリン初期分泌指数を表４に示す。なお、粉末とは、ラクトバチルス・カゼイＹＩＴ９０２９株の生菌および死菌を含む凍結乾燥粉末に対し、脱脂粉乳とトレハロースを２対１で混合した粉末を加えて上記菌数に調整したものであり、プラセボとは脱脂粉乳とトレハロースを２対１で混合したものである。なお、粉末に含まれる死菌数は、ＤＡＰＩ染色法よって粉末に含まれるラクトバチルス・カゼイの総菌数を測定し、そこから生菌数を除くことで求めた。 Test 2 (Comparative experiment)
(experimental method)
8 males with an initial insulin secretion index of less than 0.4 (Insulin early secretion index, fasting blood glucose level, and average blood glucose level after 120 minutes of glucose load were 0.24, 117 mg / dL, and 173 mg / dL, respectively) And 7 people (Insulin initial secretion index, fasting blood glucose level, and average glucose level after 120 minutes of glucose loading are 0.16, 121 mg / dL and 189 mg / dL, respectively), Lactobacillus casei viable bacteria per 2 g 4 × 10 9 cells and 2 × 10 11 cells of dead bacteria, or a placebo containing no Lactobacillus casei was ingested once a day (2 g) for 8 weeks. Table 4 shows the initial secretory index of insulin before intake and after 8 weeks. The powder is prepared by adding a powder obtained by mixing skim milk powder and trehalose in a ratio of 2 to 1 to a freeze-dried powder containing live and dead bacteria of Lactobacillus casei YIT9029 strain to adjust the number of bacteria. A placebo is a mixture of skim milk powder and trehalose in a 2 to 1 ratio. The number of dead bacteria contained in the powder was determined by measuring the total number of Lactobacillus casei contained in the powder by the DAPI staining method and excluding the number of living bacteria therefrom.
（結果）
表４に示すように、ラクトバチルス・カゼイ生菌を１日あたり４×１０9cells摂取した場合では、８週間目でインスリン初期分泌指数が下がっており、インスリン初期分泌能は改善しないことが確認された。 (result)
As shown in Table 4, it was confirmed that when Lactobacillus casei live bacteria were ingested at 4 × 10 9 cells per day, the initial insulin secretion index decreased in the 8th week, and the initial insulin secretion ability was not improved. It was done.
表４に示すように、ラクトバチルス・カゼイ生菌を１日あたり４×１０9cells摂取した場合では、８週間目でインスリン初期分泌指数が下がっており、インスリン初期分泌能は改善しないことが確認された。 (result)
As shown in Table 4, it was confirmed that when Lactobacillus casei live bacteria were ingested at 4 × 10 9 cells per day, the initial insulin secretion index decreased in the 8th week, and the initial insulin secretion ability was not improved. It was done.
Claims (9)
- 乳酸菌の生菌を１×１０10cells以上含む組成物を有効成分とするインスリン初期分泌能改善剤。 An insulin early secretory capacity improving agent comprising a composition containing 1 × 10 10 cells or more of live lactic acid bacteria as an active ingredient.
- 乳酸菌の生菌を１日あたり１×１０10cells以上摂取する請求項１記載のインスリン初期分泌能改善剤。 The insulin early secretory capacity improving agent according to claim 1, wherein 1 × 10 10 cells or more of live lactic acid bacteria are ingested per day.
- 乳酸菌が、ラクトバチルス属に属する乳酸菌である請求項１又は２記載のインスリン初期分泌能改善剤。 The agent for improving the early secretory ability of insulin according to claim 1 or 2, wherein the lactic acid bacterium is a lactic acid bacterium belonging to the genus Lactobacillus.
- 乳酸菌が、ラクトバチルス・カゼイである請求項１～３のいずれか１項記載のインスリン初期分泌能改善剤。 The insulin early secretory capacity improving agent according to any one of claims 1 to 3, wherein the lactic acid bacterium is Lactobacillus casei.
- 乳酸菌が、ラクトバチルス・カゼイ ＹＩＴ９０２９株である請求項１～４のいずれか１項記載のインスリン初期分泌能改善剤。 The insulin early secretory capacity improving agent according to any one of claims 1 to 4, wherein the lactic acid bacteria is Lactobacillus casei strain YIT9029.
- インスリン初期分泌能改善剤を製造するための、乳酸菌の生菌を１×１０10cells以上含む組成物の使用。 Use of a composition containing 1 × 10 10 cells or more of living lactic acid bacteria for producing an agent for improving insulin early secretory ability.
- インスリン初期分泌能改善に使用するための、乳酸菌の生菌を１×１０10cells以上含む組成物。 A composition containing 1 × 10 10 cells or more of live lactic acid bacteria for use in improving the initial secretory ability of insulin.
- 乳酸菌の生菌を１×１０10cells以上含む組成物を、それらを必要とする対象に有効量で投与又は摂取するインスリン初期分泌能改善方法。 A method for improving the initial secretory ability of insulin, comprising administering or ingesting an effective amount of a composition containing 1 × 10 10 cells or more of live lactic acid bacteria to a subject in need thereof.
- 乳酸菌の生菌を１日あたり１×１０10cells以上摂取する、請求項８記載のインスリン初期分泌能改善方法。 9. The method for improving the initial secretory ability of insulin according to claim 8, wherein a live lactic acid bacterium is ingested in an amount of 1 × 10 10 cells or more per day.
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| CN201680006183.5A CN107106619A (en) | 2015-01-22 | 2016-01-21 | Early secretion of insulin performance improving agent |
| JP2016570704A JP6670256B2 (en) | 2015-01-22 | 2016-01-21 | Insulin early secretory capacity improver |
| SG11201705174WA SG11201705174WA (en) | 2015-01-22 | 2016-01-21 | Agent for improving early insulin secretory capacity |
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