Mechanism of amino acid-induced skeletal muscle insulin resistance in humans
Mechanism of amino acid-induced skeletal muscle insulin resistance in humans
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DOI：
10.2337/diabetes.51.3.599
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发表时间：
2002-03-01
期刊：
影响因子：
7.7
通讯作者：
Roden, M
中科院分区：
文献类型：
--
作者：
Krebs, M;Krssak, M;Roden, M
在胰岛素抵抗状态下，血浆氨基酸浓度经常升高，富含蛋白质的饮食会损害葡萄糖代谢。本研究探讨了短期血浆氨基酸（AA）升高对全身葡萄糖处理和骨骼肌细胞胰岛素作用的影响。7名健康男性在低（类似于1.6 mmol/l）和高（类似于4.6 mmol/l）血浆AA浓度存在下，在正常血糖（5.5 mmol/l）、高胰岛素血症（430 pmol/l）、空腹胰高血糖素（65 ng/l）和生长激素（0.4 mug/l）生长抑素钳夹试验中进行了5.5 h的研究。用D-[6，6-H-2（2）]葡萄糖测定葡萄糖周转率。分别使用C-13和P-31核磁共振光谱监测肌内糖原和葡萄糖-6-磷酸（G6 P）浓度。血浆氨基酸水平升高2.1倍，全身葡萄糖代谢减少25%（P < 0.01）。肌糖原合成率下降64%（180-315分钟，24 +/- 3;对照组，67 +/- 10 mumol（.）l（-1）（.）int maximum（）; P < 0.01），这伴随着从130分钟开始的G6 P减少（Δ G6 P（260-300）（min），18 +/- 19;对照，103 +/- 33 μ mol/l，P < 0.05）。总之，血浆氨基酸水平升高通过抑制葡萄糖转运/磷酸化诱导人体骨骼肌胰岛素抵抗，导致糖原合成显著减少。
Plasma concentrations of amino acids are frequently elevated in insulin-resistant states, and a protein-enriched diet can impair glucose metabolism. This study examined effects of short-term plasma amino acid (AA) elevation on whole-body glucose disposal and cellular insulin action in skeletal muscle. Seven healthy men were studied for 5.5 h during euglycemic (5.5 mmol/l), hyperinsulinemic (430 pmol/l), fasting glucagon (65 ng/l), and growth hormone (0.4 mug/l) somatostatin clamp tests in the presence of low (similar to1.6 mmol/l) and increased (similar to4.6 mmol/l) plasma AA concentrations. Glucose turnover was measured with D-[6,6-H-2(2)]glucose. Intramuscular concentrations of glycogen and glucose-6-phosphate (G6P) were monitored using C-13 and P-31 nuclear magnetic resonance spectroscopy, respectively. A similar to2.1-fold elevation of plasma AAs reduced whole-body glucose disposal by 25% (P < 0.01). Rates of muscle glycogen synthesis decreased by 64% (180-315 min, 24 +/- 3; control, 67 +/- 10 mumol (.) l(-1) (.) min(-1); P < 0.01), which was accompanied by a reduction in G6P starting at 130 min (DeltaG6P(260-300) (min), 18 +/- 19; control, 103 +/- 33 mumol/l, P < 0.05). In conclusion, plasma amino acid elevation induces skeletal muscle insulin resistance in humans by inhibition of glucose transport/phosphorylation, resulting in marked reduction of glycogen synthesis.