α-ケトグルタル酸補給はストレプトゾトシン-高脂肪食誘発糖尿病マウスの脂肪組織における高血糖を改善し、GLUT4およびPGC-1αタンパク質の低下を抑制する

Ai Takemura^1,2, Yutaka Matsunaga^1,3, Shota Hajime¹

¹Department of Sports Sciences, The University of Tokyo, Tokyo, Japan.

Journal of nutritional science

|January 7, 2026

まとめ

α-ケトグルタル酸（AKG）は糖尿病マウスのグルコース代謝を改善する。AKG補給はミトコンドリア生合成および脂肪組織におけるグルコーストランスポーターレベルを強化し、全身のグルコース制御を助ける。

科学分野:

Biochemistry
Metabolic Research
Diabetes Mellitus

背景:

Alpha-ketoglutarate (AKG) is a key metabolic intermediate.
AKG's role in muscle and fat adaptation in diabetes requires further investigation.
Previous studies suggest AKG may enhance glucose metabolism.

研究の目的:

To investigate the effects of AKG on glucose metabolism in skeletal muscle and adipose tissue of diabetic mice.
To determine if AKG can improve the adaptation of these tissues under diabetic conditions.

主な方法:

Male ICR mice were divided into control, diabetic (high-fat diet + STZ), and diabetic + AKG groups.
AKG was administered orally to the diabetic + AKG group for 6 weeks.
Plasma glucose levels, and protein levels of GLUT4 and PGC-1α in muscle and adipose tissue were analyzed.

主要な成果:

Diabetic mice showed significantly higher plasma glucose levels compared to control and AKG-treated groups.
AKG supplementation did not alter muscle GLUT4 protein levels.
AKG attenuated decreases in PGC-1α and GLUT4 protein levels in adipose tissues of diabetic mice.

結論:

AKG supplementation improves whole-body glucose metabolism in a mouse model of diabetes.
AKG enhances mitochondrial biogenesis and glucose transporter protein levels in adipose tissue during diabetes.
AKG shows potential as a therapeutic agent for managing diabetes-related metabolic dysfunction.

キーワード:

AKG α-ケトグルタル酸 AMPK AMP活性化プロテインキナーゼ ATP5A ATP合成酵素 H+輸送ミトコンドリアF1複合体 αサブユニット脂肪組織 α-ケトグルタル酸 BAT 褐色脂肪組織 BCAA 分岐鎖アミノ酸 BCAT2 BCAAトランスアミナーゼ2 BCKA 分岐鎖ケト酸対照群糖尿病糖尿病 ELISA 酵素結合免疫吸着測定法 GLUT4 グルコーストランスポーター4 HFD 高脂肪食 HOMA-IR インスリン抵抗性定量的評価法 ICR がん研究所 NDUFB8 NADHデヒドロゲナーゼ（ユビキノン）1βサブユニット8 OXPHOS 酸化的リン酸化 PGC-1α ペルオキシソーム増殖剤応答因子γ共役因子1α PRDM16 PRD1-BF-1-RIZ1相同ドメイン含有タンパク質16 SD 標準偏差 SDHB コハク酸デヒドロゲナーゼ複合体サブユニットB STZ ストレプトゾトシン骨格筋 T2DM 2型糖尿病 TA 前脛骨筋 UCP1 脱共役タンパク質1 UQCRC2 ユビキノール-シトクロムc還元酵素コアタンパク質II mTORC1 ラパマイシン標的タンパク質複合体1

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