Cuthbertson Daniel J, Babraj John A, Mustard Kirsteen J W, Towler Mhairi C, Green Kevin A, Wackerhage Henning, Leese Graeme P, Baar Keith, Thomason-Hughes Michaela, Sutherland Calum, Hardie D Grahame, Rennie Michael J
Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.
Diabetes. 2007 Aug;56(8):2078-84. doi: 10.2337/db06-1716. Epub 2007 May 18.
Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake. The aim of this study was to determine whether AICAR stimulates muscle glucose uptake in humans. We studied 29 healthy men (aged 26 +/- 8 years, BMI 25 +/- 4 kg/m(2) [mean +/- SD]). Rates of muscle 2-deoxyglucose (2DG) uptake were determined by measuring accumulation of total muscle 2DG (2DG and 2DG-6-phosphate) during a primed, continuous 2DG infusion. The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined. Whole-body glucose disposal was compared before and during AICAR with the euglycemic-hyperinsulinemic clamp. Muscle 2DG uptake was linear over 9 h (R(2) = 0.88 +/- 0.09). After 3 h, 2DG uptake increased 2.1 +/- 0.8- and 4.7 +/- 1.7-fold in response to AICAR or bicycle exercise, respectively. AMPK alpha(1) and alpha(2) activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise. AICAR significantly increased phosphorylation of extracellular signal-regulated kinase 1/2, but phosphorylation of beta-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged. Mean whole-body glucose disposal increased by 7% with AICAR from 9.3 +/- 0.6 to 10 +/- 0.6 mg x kg(-1) x min(-1) (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal.
运动、二甲双胍、5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）和脂联素可激活啮齿动物肌肉中的AMP活化蛋白激酶（AMPK），从而增加葡萄糖摄取。本研究旨在确定AICAR是否能刺激人类肌肉对葡萄糖的摄取。我们研究了29名健康男性（年龄26±8岁，体重指数25±4kg/m²[平均值±标准差]）。通过在初始的持续2-脱氧葡萄糖（2DG）输注过程中测量总肌肉2DG（2DG和2DG-6-磷酸）的积累来确定肌肉2DG摄取率。测定了AICAR和运动对肌肉AMPK活性/磷酸化及2DG摄取的影响。在AICAR给药前和给药期间，采用正常血糖-高胰岛素钳夹技术比较全身葡萄糖处置情况。肌肉2DG摄取在9小时内呈线性（R²=0.88±0.09）。3小时后，AICAR或自行车运动分别使2DG摄取增加2.1±0.8倍和4.7±1.7倍。AICAR作用20分钟或3小时后，AMPKα1和α2活性或AMPK磷酸化未发生变化，但自行车运动后立即及3小时后AMPK磷酸化显著增加。AICAR显著增加细胞外信号调节激酶1/2的磷酸化，但β-乙酰辅酶A羧化酶、糖原合酶、蛋白激酶B或胰岛素受体底物-1水平的磷酸化未发生变化。AICAR使平均全身葡萄糖处置从9.3±0.6增加到10±0.6mg·kg⁻¹·min⁻¹，增加了7%（P<0.05）。在健康人群中，AICAR可急性刺激肌肉2DG摄取，对全身葡萄糖处置影响较小。
