EFFECT OF FATTY-ACIDS ON GLUCOSE-PRODUCTION AND UTILIZATION IN MAN
EFFECT OF FATTY-ACIDS ON GLUCOSE-PRODUCTION AND UTILIZATION IN MAN
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DOI：
10.1172/jci111133
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
DEFRONZO, RA
中科院分区：
文献类型：
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作者：
FERRANNINI, E;BARRETT, EJ;DEFRONZO, RA
自从最初提出葡萄糖脂肪酸循环以来，关于其在体内的生理学意义出现了相当大的争议。在3种受控实验条件下，在正常受试者中检查了FFA [游离脂肪酸]浓度急性生理性升高对葡萄糖产生和摄取的影响。在A组中，血浆胰岛素水平升高并维持在约100 μ U/ml，同时通过可变葡萄糖输注将血浆葡萄糖保持在空腹水平。在B组中，血浆葡萄糖浓度升高125 mg/100 ml，血浆胰岛素被钳位在λ/2。50 μ U/ml通过生长抑素和胰岛素的组合输注。在C组中，血浆葡萄糖升高至高于空腹水平200 mg/100 ml，同时用生长抑素抑制胰岛素分泌，并用胰高血糖素输注（1 ng/min. kg）。在同一受试者中重复每种方案，并结合脂质-肝素输注，以将血浆FFA水平提高1.5-2.0 μ mol/ml。对于血糖正常的高胰岛素血症（研究A），脂质输注引起总葡萄糖摄取的显著抑制（6.3 ± 0.01）。1.3 vs. 7.4 .+-。0.6 mg/min. kg，P < 0.02）。内源性葡萄糖的产生（估计的[3- 3 H]葡萄糖技术）被完全抑制与不输注脂质。对于高血糖高胰岛素血症（研究B），脂质输注也诱导了葡萄糖利用的显著损害（6.2 ± 0.01）。1.1对比9.8 .+-。1.9 mg/min. kg，P < 0.05）;尽管FFA浓度增加，内源性葡萄糖产生再次被完全抑制。在两种条件下（A和B），FFA对葡萄糖摄取的抑制率与葡萄糖总摄取率呈正相关（r = 0.69，P < 0.01）。相反，当高血糖症与相对的胰岛素减少和高胰高血糖素血症相关时（研究C），从而模拟糖尿病状态，脂质输注对葡萄糖摄取没有影响（2.9 ± 0.01）。0.2对比2.6 .+-。0.2 mg/min. kg），但显著刺激内源性葡萄糖产生（1.4 . ±. 0.5相对于0.5 ±。0.4 mg/min. kg，P < 0.005）。在与研究C相同的条件下，甘油输注产生的血浆甘油水平与用脂质-肝素获得的水平相似，提高了内源性葡萄糖的产生（1.5 ± 0.01）。0.5相对于0.7 ±。0.6 mg/min. kg，P < 0.05）。在良好胰岛素化状态下，无论是否存在高血糖症，升高的FFA水平都能有效地与葡萄糖竞争外周组织的摄取。当胰岛素缺乏时，脂解速率升高可能不是通过竞争燃料利用，而是通过内源性葡萄糖输出的增强而导致高血糖症。
Since the initial proposal of the glucose fatty acid cycle, considerable controversy has arisen concerning its physiologic significance in vivo. The effect of acute, physiologic elevations of FFA [free fatty acids] concentrations on glucose production and uptake were examined in normal subjects under 3 controlled experimental conditions. In group A, plasma insulin levels were raised and maintained at .apprx. 100 .mu.U/ml above base line by an insulin infusion, while holding plasma glucose at the fasting level by a variable glucose infusion. In group B, plasma glucose concentration was raised by 125 mg/100 ml and plasma insulin was clamped at .apprx. 50 .mu.U/ml by a combined infusion of somatostatin and insulin. In group C, plasma glucose was raised by 200 mg/100 ml above the fasting level, while insulin secretion was inhibited with somatostatin and peripheral glucagon levels were replaced with a glucagon infusion (1 ng/min .cntdot. kg). Each protocol was repeated in the same subject in combination with a lipid-heparin infusion designed to raise plasma FFA levels by 1.5-2.0 .mu.mol/ml. With euglycemic hyperinsulinemia (study A), lipid infusion caused a significant inhibition of total glucose uptake (6.3 .+-. 1.3 vs. 7.4 .+-. 0.6 mg/min .cntdot. kg, P < 0.02). Endogenous glucose production (estimated by the [3-3H]glucose technique) was completely suppressed both with and without lipid infusion. With hyperglycemic hyperinsulinemia (study B), lipid infusion also induced a marked impairment in glucose utilization (6.2 .+-. 1.1 vs. 9.8 .+-. 1.9 mg/min .cntdot. kg, P < 0.05); endogenous glucose production was again completely inhibited despite the increase in FFA concentrations. Under both conditions (A and B), the percentage inhibition of glucose uptake by FFA was positively correlated with the total rate of glucose uptake (r = 0.69, P < 0.01). In contrast, when hyperglycemia was associated with relative insulinopenia and hyperglucagonemia (study C), thus simulating a diabetic state, lipid infusion had no effect on glucose uptake (2.9 .+-. 0.2 vs. 2.6 .+-. 0.2 mg/min .cntdot. kg) but markedly stimulated endogenous glucose production (1.4 .+-. 0.5 vs. 0.5 .+-. 0.4 mg/min .cntdot. kg, P < 0.005). Under the same conditions as study C, a glycerol infusion producing plasma glycerol levels similar to those achieved with lipid-heparin, enhanced endogenous glucose production (1.5 .+-. 0.5 vs. 0.7 .+-. 0.6 mg/min .cntdot. kg, P < 0.05). In the well-insulinized state, raised FFA levels effectively compete with glucose for uptake by peripheral tissues, regardless of the presence of hyperglycemia. When insulin is deficient, elevated rates of lipolysis may contribute to hyperglycemia not by competition for fuel utilization, but through an enhancement of endogenous glucose output.