JPWO2018179441A1 - インスリン抵抗性の悪化予防または改善剤 - Google Patents
インスリン抵抗性の悪化予防または改善剤 Download PDFInfo
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- JPWO2018179441A1 JPWO2018179441A1 JP2019508500A JP2019508500A JPWO2018179441A1 JP WO2018179441 A1 JPWO2018179441 A1 JP WO2018179441A1 JP 2019508500 A JP2019508500 A JP 2019508500A JP 2019508500 A JP2019508500 A JP 2019508500A JP WO2018179441 A1 JPWO2018179441 A1 JP WO2018179441A1
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- insulin resistance
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- obesity
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Abstract
Description
(i)グルコースクランプ法(Defronzo RAら、Am J Physiol、第237巻、E214−E223、1979年)、
(ii)steady state plasma glucose法(Harano Yら、J Clin Endoclinol Metab 第45巻、第1124−1127頁、1977年)、
(iii)minimal model法(Bergman RNら、Diabetes、第38巻、第1512−1527頁、1989年)、
(iv)HOMA法(Matthews DRら、Diabetologia、第28巻、第412−419頁、1985年)、
(v)空腹時血糖値、
(vi)空腹時血中インスリン濃度、
(vii)経口ブドウ糖負荷試験時の血漿インスリン濃度(老松 寛ら、糖尿病、第43巻 第3号、第205−212頁、2000年)。
式1:HOMA−IR=(空腹時血中インスリン濃度(μU/mL)×空腹時血糖値(mg/dL))/405
同一被検者におけるHOMA−IRの増大はインスリン抵抗性の増大を意味し、HOMA−IRの減少はインスリン抵抗性の減少を意味する。よって、1−ケストースを摂取することによりHOMA−IRの増大を抑制できれば、本発明によりインスリン抵抗性の悪化を予防できたと判断することができる。また、1−ケストースを摂取することにより、摂取前よりHOMA−IRを低い値とすることができれば、本発明によりインスリン抵抗性を改善できたと判断することができる。
(1)ラットの飼育
1−ケストースを0、0.5、1、2.5および5質量%となるように配合した飼料を日本クレア社に委託して調製した。飼料の組成を下記に示す。
《飼料の組成》(単位は質量%)
コーンスターチ:39.7486、ミルクカゼイン:20、アルファ化コーンスターチ:13.2、グラニュー糖またはグラニュー糖および1−ケストース:10、精製大豆油:7、セルロースパウダー:5、ミネラルミックス:3.5、ビタミンミックス:1、L−シスチン:0.3、重酒石酸コリン:0.25、第3ブチルヒドロキノン:0.0014。
《式1》ヒト成人における1日の1−ケストース摂取量(g/kg体重)=ラットにおける1日の1−ケストースの摂取量(g/kg体重)×6/37
そこで、式1により、ラットにおける1日の1−ケストース摂取量を、ヒト成人におけるものに換算した。その結果を表1に示す。
本実施例1(1)の各群のラットの下大静脈から血液を採取し、10000×gにて遠心分離して血清を得た。得られた血清について、ELISA法によりインスリンの濃度を、グルコースオキシダーゼ法によりグルコースの濃度をそれぞれ測定し、各群毎に平均値および標準偏差を算出した。その結果を表1に示す。また、血清インスリン濃度については図1に、血糖値については図2に、それぞれ棒グラフを示す。
(1)ラットの飼育
SDラット(日本エスエルシー社)を6〜8匹ずつ4つの群に分け、A〜D群とした。飼育期間中、A群およびC群には、水道水を自由飲水させた。一方、B群およびD群には、精製水に2質量%となるように1−ケストースを溶解した溶液を自由飲水させることにより、1−ケストースを摂取させた。また、A群およびB群には、「普通食」としてD12492J(リサーチダイエット社)を、C群およびD群には「高脂肪食」としてD12492(リサーチダイエット社)をそれぞれ自由摂取させた。その他の飼育条件は実施例1(1)と同様にして、135日間飼育した。飼料の組成を下記に示す。
カゼイン:200、L−シスチン:3、コーンスターチ:506.2、マルトデキストリン 10:125、スクロース:68.8、セルロース BW200:50、精製大豆油:25、ラード:20、ミネラルミックス S10026:10、リン酸二カルシウム:13,炭酸カルシウム:5.5、クエン酸カリウム1水和物:16.5、ビタミンミックス V10001:10、重酒石酸コリン:2、黄色合成着色料(FD&C Yellow Dye#1):0.04、青色合成着色料(FD&C Blue Dye#1):0.01。
《高脂肪食の飼料(D12492)の組成》(単位は質量%)
カゼイン:200、L−シスチン:3、マルトデキストリン 10:125、スクロース:68.8、セルロース BW200:50、精製大豆油:25、ラード:245、ミネラルミックス S10026:10、リン酸二カルシウム:13,炭酸カルシウム:5.5、クエン酸カリウム1水和物:16.5、ビタミンミックス V10001:10、重酒石酸コリン:2、青色合成着色料(FD&C Blue Dye#1):0.05。
本実施例2(1)の各群のラットについて、飼育期間中の1週間経過毎に体重を測定して各群毎に平均値を算出し、折れ線グラフに表した。その結果を図3に示す。なお、飼育期間開始時の各群の体重(g)は、A群が272±5、B群が268±6、C群が272±3、D群が269±3であった。
(1)ラットの飼育
2型糖尿病の病態を呈するモデル動物であるOLETF(Otsuka Long-Evans Tokushima Fatty)ラット(日本エスエルシー社)と、そのコントロールであるLETO(Long-Evans Tokushima Otsuka)ラット(日本エスエルシー社)とを用意した。LETOラットを5匹ずつ2つの群に分け、A群およびB群とした。また、OLETFラットを8匹ずつ3つの群に分け、C群、D群およびE群とした。飼育期間中、A群およびC群には実施例1(1)の「1−ケストースを配合しない飼料」を、B群およびE群には「1−ケストースを5質量%となるように配合した飼料」を、D群には「1−ケストースを1質量%となるように配合した飼料」を、それぞれ自由摂取させた。その他の飼育条件は実施例1(1)と同様にして、14日間飼育した。
本実施例3(1)の各群のラットについて、実施例1(2)に記載の方法により血漿インスリン濃度および血糖値を測定して各群毎に平均値および標準偏差を算出した。その結果を表3に示す。また、血漿インスリン濃度については図6に、血糖値については図7に、それぞれ棒グラフを示す。
また、LETOラットの間で比較すると、血漿インスリン濃度は、A群と比較してB群で小さかった。すなわち、1−ケストースを摂取したLETOラットでは、1−ケストースを摂取しないLETOラットと比較して、血漿インスリン濃度が小さかった。
また、OLETFラットの間で比較すると、血漿インスリン濃度の大きさは、C群>D群>E群の順であった。すなわち、1−ケストースを摂取したOLETFラットでは、1−ケストースを摂取しないOLETFラットと比較して血漿インスリン濃度が小さく、1−ケストースの摂取量が大きいほど、血漿インスリン濃度が小さかった。
Claims (6)
- 1−ケストースを有効成分とするインスリン抵抗性の悪化予防または改善剤。
- 糖尿病、耐糖能異常、肥満症、高脂血症、動脈硬化、高血圧症、心疾患またはメタボリック症候群の予防または治療に用いられることを特徴とする、請求項1に記載のインスリン抵抗性の悪化予防または改善剤。
- 1−ケストースを有効成分とするインスリン抵抗性の悪化予防または改善用食品組成物。
- ヒトまたは動物に1−ケストースを摂取させることにより、前記ヒトまたは動物におけるインスリン抵抗性の悪化を予防またはインスリン抵抗性を改善する工程を有する、インスリン抵抗性の悪化予防または改善方法。
- 糖尿病、耐糖能異常、肥満症、高脂血症、動脈硬化、高血圧症、心疾患またはメタボリック症候群を罹患しているヒトもしくは動物に、1−ケストースを摂取させることにより、前記ヒトまたは動物におけるインスリン抵抗性を改善する工程を有する、糖尿病、耐糖能異常、肥満症、高脂血症、動脈硬化、高血圧症、心疾患またはメタボリック症候群の治療方法。
- 糖尿病、耐糖能異常、肥満症、高脂血症、動脈硬化、高血圧症、心疾患またはメタボリック症候群を罹患する可能性があるヒトもしくは動物に、1−ケストースを摂取させることにより、前記ヒトまたは動物におけるインスリン抵抗性の悪化を予防する工程を有する、糖尿病、耐糖能異常、肥満症、高脂血症、動脈硬化、高血圧症、心疾患またはメタボリック症候群の予防方法。
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