Felig P, Wahren J
J Clin Invest. 1971 Aug;50(8):1702-11. doi: 10.1172/JCI106659.
Splanchnic exchange of glucose, 20 individual amino acids, lactate, and pyruvate was studied in normal subjects in the postabsorptive state and after stimulation of endogenous insulin secretion by infusion of glucose at two dose levels. In the basal state, mean splanchnic glucose production was 3.4 mg/kg per min. A net uptake of lactate, pyruvate, and nine amino acids was observed, with alanine accounting for half of the total splanchnic-amino acid extraction. Infusion of glucose at 25 mg/kg per min for 20 min resulted in a fivefold increase in arterial insulin levels and in reversal of splanchnic glucose balance to a net uptake. Splanchnic uptake of alanine, glycine, phenylalanine, lactate, and pyruvate fell by 30-60% due to a reduction in fractional extraction of these substrates, inasmuch as their arterial concentrations did not decline.Administration of glucose at 2 mg/kg per min for 45 min resulted in a 19 mg/100 ml increase in arterial glucose concentration and a doubling of arterial insulin levels. Despite the small increment in insulin, hepatic glucose production fell by 85%. Splanchnic exchange of amino acids, lactate, and pyruvate was unaltered. Estimated total glucose utilization during the infusion was no greater than in the basal state, indicating lack of stimulation of peripheral glucose uptake. IT IS CONCLUDED THAT: (a) inhibition of hepatic glucose production associated with glucose infusion and large increments in insulin levels occurs in the absence of a decrease in the concentration of circulating gluconeogenic substrate, suggesting an hepatic rather than peripheral effect; (b) the liver is the primary target organ whereby glucose homeostasis is achieved with small increments in insulin; (c) the relatively greater sensitivity of the liver's response to insulin as compared with an effect of insulin on the peripheral tissues, may be a consequence of the higher levels of endogenous insulin in portal as compared with peripheral blood.
研究了正常受试者在吸收后状态以及通过输注两种剂量水平的葡萄糖刺激内源性胰岛素分泌后，葡萄糖、20种单个氨基酸、乳酸和丙酮酸的内脏交换情况。在基础状态下，平均内脏葡萄糖生成量为每分钟3.4毫克/千克。观察到有乳酸、丙酮酸和9种氨基酸的净摄取，其中丙氨酸占内脏氨基酸总摄取量的一半。以每分钟25毫克/千克的速度输注葡萄糖20分钟，导致动脉胰岛素水平增加了五倍，并使内脏葡萄糖平衡逆转至净摄取状态。由于这些底物的分数提取减少，丙氨酸、甘氨酸、苯丙氨酸、乳酸和丙酮酸的内脏摄取量下降了30%至60%，因为它们的动脉浓度并未下降。以每分钟2毫克/千克的速度输注葡萄糖45分钟，导致动脉葡萄糖浓度增加19毫克/100毫升，动脉胰岛素水平翻倍。尽管胰岛素增加幅度较小，但肝脏葡萄糖生成量下降了85%。氨基酸、乳酸和丙酮酸的内脏交换未发生改变。输注期间估计的总葡萄糖利用率不高于基础状态，表明外周葡萄糖摄取未受到刺激。得出以下结论：(a) 在循环糖异生底物浓度未降低的情况下，与葡萄糖输注和胰岛素水平大幅增加相关的肝脏葡萄糖生成受到抑制，这表明是肝脏而非外周的作用；(b) 肝脏是通过胰岛素小幅增加来实现葡萄糖稳态的主要靶器官；(c) 与胰岛素对外周组织的作用相比，肝脏对胰岛素反应的相对更高敏感性可能是门静脉中内源性胰岛素水平高于外周血的结果。
