Insulin and hyperaminoacidemia regulate by a different mechanism leucine turnover and oxidation in obesity
Insulin and hyperaminoacidemia regulate by a different mechanism leucine turnover and oxidation in obesity
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DOI：
10.1152/ajpendo.1996.270.2.e273
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发表时间：
1996-02-01
影响因子：
5.1
通讯作者：
DeFronzo, RA
中科院分区：
文献类型：
--
作者：
Luzi, L;Castellino, P;DeFronzo, RA
7例正常糖耐量肥胖者[理想体重(IBW) = 161%]和18例对照组（IBW = 102%）分别给予10和40 mU的正糖胰岛素。(2)。min（-1）技术，[C-14]亮氨酸输注，以及间接量热法，以检查葡萄糖代谢方面的胰岛素抵抗是否扩展到氨基酸/蛋白质代谢。在基础状态下，肥胖和对照组的血浆总氨基酸和亮氨酸浓度、内源性亮氨酸通量（ELF）、亮氨酸氧化（LO）和非氧化亮氨酸处置（NOLD）相似。在低(10 mU。(2)。min(-1))-或更高（40 mU）。(2)。在min（-1）剂量胰岛素钳夹研究中，与对照组相比，肥胖者胰岛素介导的葡萄糖摄取减少（P < 0.01）。在高剂量胰岛素钳夹步骤的最后一个小时，与对照组相比，肥胖组血浆总氨基酸、支链氨基酸和亮氨酸浓度的下降受到损害（P < 0.01）。然而，两组对ELF和NOLD的抑制相似。低剂量胰岛素钳夹时，血浆亮氨酸浓度下降、LO、ELF均受影响（P < 0.01）。在第二项研究中，两组的血浆总氨基酸浓度都增加了两到三倍。在这些低血浆胰岛素/高氨基酸水平的条件下，肥胖者和对照组的LO和NOLD增加相似。总之，胰岛素抵抗是肥胖症中葡萄糖和蛋白质代谢的共同特征。蛋白质代谢缺陷的特征是胰岛素抑制蛋白质水解的能力受损；高氨基酸酸血症对蛋白质合成的刺激作用在肥胖中是完整的。
Seven normal glucose-tolerant obese subjects [ideal body weight (IBW) = 161%] and 18 controls (IBW = 102%) were studied with the euglycemic insulin damp (10 and 40 mU . m(-2). min(-1)) technique, [C-14]leucine infusion, and indirect calorimetry to examine if the insulin resistance with respect to glucose metabolism extends to amino acid/protein metabolism. In the basal state, total plasma amino acid and leucine concentrations, endogenous leucine flux (ELF), leucine oxidation (LO), and nonoxidative leucine disposal (NOLD) were similar in obese and control subjects. During both low (10 mU . m(-2). min(-1))- and higher (40 mU . m(-2). min(-1))-dose insulin clamp studies, insulin-mediated glucose uptake was reduced in obese vs. control subjects (P < 0.01). During the last hour of the higher-dose insulin clamp step, the decrease in total plasma amino acids, branched-chain amino acids, and leucine concentration was impaired in obese vs. control subjects (P < 0.01). However, suppression of ELF and NOLD was similar in both groups. During the low-dose insulin clamp, the decrease in plasma leucine concentration, LO, and ELF all were impaired (P < 0.01). A second study was performed in which the total plasma amino acid concentration was increased two- to threefold in both groups. Under these conditions of low plasma insulin/high amino acid levels, LO and NOLD increased similarly in obese and control subjects. In conclusion, insulin resistance is a common feature of both glucose and protein metabolism in obesity. The defect in protein metabolism is characterized by an impairment of the ability of insulin to inhibit proteolysis; the stimulatory effect of hyperaminoacidemia on protein synthesis is intact in obesity.