高密度リポプロテインは,2型糖尿病患者におけるグルコース代謝を調節する
Brian G Drew1, Stephen J Duffy, Melissa F Formosa
1Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
Circulation
|April 8, 2009
まとめ
再構成された高密度リポプロテイン (HDL) は,インスリンを増加させ,筋肉のAMP活性化タンパク質キナーゼを活性化することによって,タイプ2糖尿病における血糖を低下させます. これは,HDL療法は,心血管の利点を超えて,2型糖尿病を治療する可能性があることを示唆しています.
科学分野:
- メタボリックシンドローム
- 心血管リスク 心血管リスク
- グルコースの代謝
背景:
- 高密度低脂質タンパク質 (HDL) は,心血管疾患のリスク増加と代謝症候群に関連しています.
- 骨格筋におけるインスリンとAMP活性化タンパク質キナーゼ (AMPK) によるグルコース代謝の調節におけるHDLの役割が調査されました.
研究 の 目的:
- 2型糖尿病患者におけるグルコース代謝に対する再構成HDL (rHDL) の影響を調査する.
- rHDLが骨格筋におけるAMP活性化タンパク質キナーゼ (AMPK) を活性化しているかどうかを判断する.
主な方法:
- 2型糖尿病の13人の患者を対象とした,ダブルブラインド,プラセボ対照のクロスオーバー研究.
- rHDL (80 mg/kg) またはプラセボを静脈内投与する.
- 骨格筋生検における血糖,インスリン,AMPK経路活性化 (アセチル-CoAカルボキシラーゼβリン酸化) の測定.
- 人間の骨格筋細胞培養におけるグルコース吸収の評価.
主要な成果:
- rHDLはプラセボと比較してプラズマグルコースを有意に低下させた.
- rHDLは血インスリンを増加させ,ホメオスタシスモデルの評価ではベータ細胞機能指数である.
- rHDLは,骨格筋におけるAMP活性化タンパク質キナーゼ (AMPK) 経路を活性化させた.
- HDLとアポリポプロテインAIは,ヒトの骨格筋細胞のグルコース吸収を増加させた.
結論:
- rHDLは,インスリン分泌を強化し,骨格筋のAMPKを活性化することによって,2型糖尿病患者の血糖を効果的に低下させます.
- HDLを高める治療法は,2型糖尿病の治療の可能性を示しており,動脈硬化管理における既定の役割を超えて拡大しています.
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