CONTRIBUTION OF MUSCLE AND LIVER TO GLUCOSE-FATTY ACID CYCLE IN HUMANS
CONTRIBUTION OF MUSCLE AND LIVER TO GLUCOSE-FATTY ACID CYCLE IN HUMANS
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DOI：
10.1152/ajpendo.1993.264.4.e599
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发表时间：
1993-04-01
影响因子：
--
通讯作者：
GROOP, L
中科院分区：
文献类型：
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作者：
SALORANTA, C;KOIVISTO, V;GROOP, L
为了研究游离脂肪酸（FFA）水平升高对肝脏葡萄糖生成（HGP）以及葡萄糖代谢的氧化和非氧化途径的影响，12名健康受试者参加了两项正糖胰岛素夹夹研究，分别在输注脂内加肝素和不输注脂内加肝素的情况下进行。为了阐明骨骼肌在这种假定的相互作用中的作用，我们进行了肌肉活检，以测量糖原合成酶（GS）、丙酮酸脱氢酶（PDH）和肉毒碱棕榈酰转移酶（CPT）的活性。脂质内加肝素的输注引起血浆FFA浓度和脂质氧化速率（通过间接量热法测量）的增加，而胰岛素不抑制这种增加。胰岛素对HGP的抑制作用因血浆游离脂肪酸水平升高而受损。此外，血浆FFA的增加与总葡萄糖代谢降低20%相关（P < 0.01），这完全归因于葡萄糖氧化速率的降低。虽然胰岛素可以增加GS的活性，但血浆FFA的升高对这一糖原合成的关键酶没有影响。此外，PDH和CPT的活性不受FFA升高的影响，这表明在当前条件下，骨骼肌中的氧化过程不是手术中葡萄糖-脂肪酸循环的主要目标。综上所述，这些数据表明FFA和葡萄糖代谢之间的相互作用也涉及胰岛素对HGP的抑制受损。
To examine the influence of elevated free fatty acid (FFA) levels on hepatic glucose production (HGP) and oxidative and nonoxidative pathways of glucose metabolism, 12 healthy subjects participated in two euglycemic insulin-clamp studies performed with and without infusion of Intralipid plus heparin. To elucidate the role of skeletal muscle in this putative interaction, we performed muscle biopsies for the measurement of activities of glycogen synthase (GS), pyruvate dehydrogenase (PDH), and carnitine palmitoyltransferase (CPT). Infusion of Intralipid plus heparin caused an increase in plasma FFA concentrations and rate of lipid oxidation (measured by indirect calorimetry) that was not inhibited by insulin. Suppression of HGP by insulin was impaired by elevated plasma FFA levels. Furthermore, the increase in plasma FFA was associated with a 20% reduction in total glucose metabolism (P < 0.01), which was completely accounted for by a reduction in the rate of glucose oxidation. Although the fractional activity of GS was increased by insulin, elevation of plasma FFA had no influence on this key enzyme of glycogen synthesis. In addition, the activities of PDH and CPT were uninfluenced by the elevation of FFA, suggesting that oxidative processes in skeletal muscle were not a major target for the operative glucose-fatty acid cycle under the current conditions. Taken together, the data indicate that the interaction between FFA and glucose metabolism also involves impaired suppression of HGP by insulin.