JP2008214274A - すい臓β細胞インスリン分泌能促進剤および体内組織細胞グルコース取り込み能促進剤 - Google Patents
すい臓β細胞インスリン分泌能促進剤および体内組織細胞グルコース取り込み能促進剤 Download PDFInfo
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Abstract
【解決手段】非発酵型ルイボス茶の特異な成分であるアスパラチンに膵β細胞インスリン分泌促進作用および骨格筋細胞グルコース取込み促進作用を認め、本発明を完成した。
【選択図】なし
Description
(1)アスパラチンを有効成分とする膵β細胞インスリン分泌促進剤、
(2)アスパラチンを有効成分とする体内組織細胞によるグルコース取込み促進剤、
(3)体内組織細胞が骨格筋細胞であることを特徴とする(2)記載のグルコース取込み促進剤
に関するものである。
アスパラチンは、次のような構造式を有している。
非発酵型ルイボス茶より、アスパラチンを精製した。アスパラチンは、287nmに特異的な極大吸収を示すが、これを指標としてHPLCで分析し精製を行った。アスパラチンをエタノールにてソックスレー抽出し、濃縮、ヘキサンを添加し、ヘキサン層と含水エタノール層を形成するまで脱イオン水を攪拌しながら添加した。含水エタノール層を濃縮、脱エタノール後、吸着樹脂にアスパラチンを吸着させた。吸着樹脂を脱イオン水で洗浄後、吸着したアスパラチンをエタノールで溶出させ、これをさらにシリカゲル、HP20SS吸着樹脂、ウィンタリング、結晶化などで精製し、純度96.3%のアスパラチンを得た。
膵β細胞インスリン分泌能促進作用は、ラット膵臓β細胞由来のRIN-5Fを用いて測定した。
RIN-5F 細胞(ATCC、CRL-2058)は、L-グルタミン(和光純薬社製)300mg/L、NaHCO3(和光純薬社製)1.8〜3.0g/L、ストレプトマイシン100μg/L、ペニシリン100 units/mlを添加し、10%ウシ胎児血清(FBS)含有RPMI 1640培地(10%FBS/RPMI 1640) を用いて、37℃、5%CO2/95%空気下CO2インキュベーター(Model IT43、ヤマト科学)で培養した。
RIN-5細胞から分泌されるインスリン量の測定は、Nomuraらの方法を一部改変して行った (Bioorg. Med. Chem. 11, 3807-3813 (2003)) 。
グルコース取り込み能促進作用は、ラット由来L6筋芽細胞を用いて測定した。
L6筋芽細胞は、Yagasakiらの方法で培養した。(Cytotechnology, 43, 97-103 (2003))
L-グルタミン(和光純薬工業、大阪)584 mg/l、NaHCO3、1.2〜2.0 g/l、ストレプトマイシン100 μg/l、ペニシリン100 units/mlを添加した10%FBS/DMEM培地(日水製薬、東京)を用いて、37℃、5%CO2/95%空気下CO2インキュベーターで維持培養した。
L6筋管細胞に取り込まれたグルコース量の測定は、Doiらの方法(Biochem. Biophys. Res. Commun., 312, 1111-1117(2003))に基づき、一部改変して行った。
[動物飼育]
db/db, db/+, +/+系雄マウス(日本チャールス・リバー社製)を5週齢で購入し、明期8:00〜20:00、室温22±1℃、相対湿度60±5%の空調飼育室内で5室ケージを用いて飼育した。db/db系雄マウスは糖尿病モデルマウスであり、db/+, +/+系雄マウスは正常形質のマウスである。これらマウスに固型飼料(CE-2, CLEA JAPAN社製)を与え、水道水と共に3日間自由摂取させた。その後、20%カゼイン食(20C,AIN-93処方)に切り換え、さらに4日間飼育した後、db/dbマウスは2群に分けた。6週齢となったdb/dbマウスを血糖値、体重共に有意差が生じないよう2群に分け、対照群(n=6)には20Cを、実験群(n=4)には20Cに0.1%アスパラチンを添加した飼料を与え3週間飼育した。その後は,0.2%アスパラチンを添加した飼料を与えて飼育した。
空腹時血糖値の測定は1〜2週に一度行った。午前9時に飼料を取り除き(水は与えたまま)4時間の絶食後、メスにより尾静脈を軽く刺傷した後、血液を目盛り付きガラス毛細管マイクロピペット(10 ml用、Drummond Scientific 社製)を用いて吸引し採血した。吸引採取された血液は、40 mlの超純水が入った1.5 mlマイクロテストチューブの中に吹き込み、溶血させ、氷中で保存した。
アスパラチン投与5週後、11週齡のdb/dbマウスを35日目の午後8時から36日目の午前11時まで15時間絶食後、超純(MQ)水に溶解したアスパラチンを20 mg/ml/100 g体重となるようにマウスに経口投与した。対照群には超純水のみ投与した。その2時間後に血液を採取し(図4、0 h値)、両群のdb/dbマウスに超純水に溶解したグルコース溶液を200mg/ml/100 g体重となるようにマウスの腹腔内に注射した。グルコースを負荷してから、0.5、1.0、1.5、2.0時間後の血液を経時的に採取した。血液採取法および測定法は上記に準じた。
Claims (3)
- アスパラチンを有効成分とする膵β細胞インスリン分泌促進剤。
- アスパラチンを有効成分とする体内組織細胞によるグルコース取込み促進剤。
- 体内組織細胞が骨格筋細胞であることを特徴とする請求項2記載のグルコース取込み促進剤。
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JP2017109971A (ja) * | 2015-12-18 | 2017-06-22 | 花王株式会社 | PPARδ活性化剤 |
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JP2010520913A (ja) * | 2007-03-12 | 2010-06-17 | サズセ アーペーエス | ルイボスの抗糖尿病性抽出物 |
JP2017109971A (ja) * | 2015-12-18 | 2017-06-22 | 花王株式会社 | PPARδ活性化剤 |
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