Lillioja S, Bogardus C, Mott D M, Kennedy A L, Knowler W C, Howard B V
Pheonix Clinical Research Section, Southwestern Field Studies, Phoenix, Az 85016, USA.
J Clin Invest. 1985 Apr;75(4):1106-15. doi: 10.1172/JCI111804.
To assess the possible effects of lipid metabolism on insulin-mediated glucose disposal, 18 nondiabetic Pima Indian women (age 18-35 yr) were studied using 1-14C-palmitate infusion to measure free fatty acid turnover rate followed by a euglycemic clamp (clamp) to measure in vivo insulin-mediated glucose disposal (M). Indirect calorimetry was performed in the basal state and during the clamp. This was used to assess glucose oxidation rate, lipid oxidation rate, and to calculate nonoxidative glucose disposal (storage). Basal and clamp lipid oxidation rate correlated with basal plasma free fatty acid concentration (r = 0.81, P less than or equal to 0.0001, r = 0.67, P less than 0.003, respectively). The fall in lipid oxidation was highly correlated with the increase in glucose oxidation during the insulin infusion (r = 0.96, P less than or equal to 0.0001). The clamp lipid oxidation rate negatively correlated with the glucose oxidation rate (r = -0.85, P less than 0.0001) and with the M value (r = -0.60, P less than 0.01) but was not correlated with the clamp glucose storage (r = -0.2, P = 0.4). On the other hand, glucose storage appeared to make a greater contribution to the difference in M value between the upper and lower extremes of M than did glucose oxidation, as evidenced by an increase in glucose storage of 0.59 mg/kg fat-free mass times minute per 1 mg/kg fat-free mass times minute increase in glucose disposal. The M value was negatively correlated with obesity as measured by percent body fat (r = -0.64, P less than 0.004), but neither basal free fatty acid concentration, basal free fatty acid turnover, basal lipid oxidation, nor clamp lipid oxidation correlated with percent body fat. We conclude that an interaction of lipid and glucose metabolism in a glucose fatty acid cycle, as proposed by Randle et al. (1), may be operative in the regulation of glucose oxidation in man. The disposal of glucose however has two components. The storage component does not appear to be associated with lipid oxidation in the way that the oxidative component is and may be regulated by a different mechanism. Since the results show that the glucose storage component plays a significant role in distinguishing between those with low and high M values, we suggest that the glucose fatty acid cycle can, at best, only partially explain impaired in vivo insulin-mediated glucose disposal. Furthermore, the data suggest that the impact of obesity on in vivo insulin resistance appears to be mediated by factors other than changes in lipid availability or metabolism.
为评估脂质代谢对胰岛素介导的葡萄糖处置的可能影响，对18名非糖尿病皮马印第安女性（年龄18 - 35岁）进行了研究。采用输注1-14C-棕榈酸酯来测量游离脂肪酸周转率，随后进行正常血糖钳夹试验（钳夹试验）以测量体内胰岛素介导的葡萄糖处置（M）。在基础状态和钳夹试验期间进行间接测热法。这用于评估葡萄糖氧化率、脂质氧化率，并计算非氧化葡萄糖处置（储存）。基础和钳夹试验时的脂质氧化率与基础血浆游离脂肪酸浓度相关（分别为r = 0.81，P≤0.0001；r = 0.67，P＜0.003）。在胰岛素输注期间，脂质氧化的下降与葡萄糖氧化的增加高度相关（r = 0.96，P≤0.0001）。钳夹试验时的脂质氧化率与葡萄糖氧化率呈负相关（r = -0.85，P＜0.0001），与M值呈负相关（r = -0.60，P＜0.01），但与钳夹试验时的葡萄糖储存无相关性（r = -0.2，P = 0.4）。另一方面，葡萄糖储存似乎比葡萄糖氧化对M值高低极端之间差异的贡献更大，每1mg/kg去脂体重每分钟葡萄糖处置增加量会使葡萄糖储存增加0.59mg/kg去脂体重每分钟，这证明了这一点。M值与以体脂百分比衡量的肥胖呈负相关（r = -0.64，P＜0.004），但基础游离脂肪酸浓度、基础游离脂肪酸周转率、基础脂质氧化或钳夹试验时的脂质氧化均与体脂百分比无相关性。我们得出结论，正如兰德尔等人（1）所提出的，葡萄糖 - 脂肪酸循环中脂质和葡萄糖代谢的相互作用可能在人体葡萄糖氧化的调节中起作用。然而，葡萄糖处置有两个组成部分。储存部分似乎不像氧化部分那样与脂质氧化相关，可能受不同机制调节。由于结果表明葡萄糖储存部分在区分低M值和高M值个体方面起重要作用，我们认为葡萄糖 - 脂肪酸循环充其量只能部分解释体内胰岛素介导的葡萄糖处置受损。此外，数据表明肥胖对体内胰岛素抵抗的影响似乎是由脂质可用性或代谢变化以外的因素介导的。
