Onay-Besikci Arzu, Wagg Cory, Lopaschuk Timothy P, Keung Wendy, Lopaschuk Gary D
Ankara University, Faculty of Pharmacy, Department of Pharmacology, Ankara, Turkey.
Basic Res Cardiol. 2007 Sep;102(5):436-44. doi: 10.1007/s00395-007-0661-4. Epub 2007 May 29.
Alpha-lipoic acid (ALA) is a naturally occurring enantiomer of lipoic acid and is a cofactor of key metabolic enzyme complexes catalyzing the decarboxylation of alpha-keto acids. It was recently shown that ALA increases insulin sensitivity by activating AMP-activated protein kinase (AMPK) in skeletal muscle. Also, administration of ALA to obese rats increases insulin-stimulated glucose uptake in the whole body. We investigated the metabolic effects of ALA on isolated working rat hearts. ALA (500 microM) stimulated glucose oxidation (157+/-31 nmol.dry wt(-1).min(-1) in control vs 315+/-63 nmol.dry wt(-1).min(-1) in ALA-treated, p<0.05) without affecting glycolysis, lactate oxidation, or palmitate oxidation. Cardiac work was not affected by ALA treatment. The effect of ALA on glucose oxidation was not associated with an activation of AMPK. AMPK activity was 190+/-14 pmol.mg protein(-1).min(-1) in control vs 190+/-16 pmol.mg protein(-1).min(-1) in ALA-treated hearts. This study shows that ALA stimulates glucose oxidation in isolated working rat hearts independent of AMPK activation. The beneficial effects of ALA treatment in diabetic patients may be at least in part related to its effect on glucose metabolism.
α-硫辛酸（ALA）是硫辛酸的一种天然对映体，是催化α-酮酸脱羧反应的关键代谢酶复合物的一种辅助因子。最近有研究表明，ALA通过激活骨骼肌中的AMP激活蛋白激酶（AMPK）来提高胰岛素敏感性。此外，给肥胖大鼠施用ALA可增加全身胰岛素刺激的葡萄糖摄取。我们研究了ALA对离体工作大鼠心脏的代谢影响。ALA（500微摩尔）刺激了葡萄糖氧化（对照组为157±31纳摩尔·干重⁻¹·分钟⁻¹，ALA处理组为315±63纳摩尔·干重⁻¹·分钟⁻¹，p<0.05），而不影响糖酵解、乳酸氧化或棕榈酸氧化。心脏做功不受ALA处理的影响。ALA对葡萄糖氧化的作用与AMPK的激活无关。对照组心脏的AMPK活性为190±14皮摩尔·毫克蛋白⁻¹·分钟⁻¹，ALA处理组心脏为190±16皮摩尔·毫克蛋白⁻¹·分钟⁻¹。本研究表明，ALA在离体工作大鼠心脏中刺激葡萄糖氧化，且与AMPK激活无关。ALA治疗对糖尿病患者的有益作用可能至少部分与其对葡萄糖代谢的影响有关。
