DEMONSTRATION OF A CRITICAL ROLE FOR FREE FATTY-ACIDS IN MEDIATING COUNTERREGULATORY STIMULATION OF GLUCONEOGENESIS AND SUPPRESSION OF GLUCOSE-UTILIZATION IN HUMANS
DEMONSTRATION OF A CRITICAL ROLE FOR FREE FATTY-ACIDS IN MEDIATING COUNTERREGULATORY STIMULATION OF GLUCONEOGENESIS AND SUPPRESSION OF GLUCOSE-UTILIZATION IN HUMANS
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DOI：
10.1172/jci116746
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发表时间：
1993-10-01
影响因子：
15.9
通讯作者：
BOLLI, GB
中科院分区：
文献类型：
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作者：
FANELLI, C;CALDERONE, S;BOLLI, GB
体外研究表明，FFA与葡萄糖竞争作为肌肉中的氧化燃料，此外，还刺激肝脏中的再生。在低血糖的反调节过程中，血浆FFA增加，这与葡萄糖产生的增加和葡萄糖利用的抑制有关。为了检验FFA介导反调节过程中发生的葡萄糖代谢变化的假设，我们研究了阿昔莫司（一种脂解抑制剂）对葡萄糖产生和利用（[3-H-3]葡萄糖）的影响，以及胰岛素诱导的低血糖期间[U-C-14]-丙氨酸掺入葡萄糖的影响。8名正常志愿者在两种情况下输注胰岛素8小时以产生中度低血糖（约3 mM），首先不使用阿昔莫司（对照），然后使用阿昔莫司给药（在60和240 min时口服250 mg）。尽管血浆胰岛素浓度相同，但在阿昔莫司实验（葡萄糖钳夹技术）中必须输注葡萄糖，以维持与对照实验相同的血浆葡萄糖浓度。阿昔莫司完全阻止了脂解中的反调节增加，因此在最后4小时血浆FFA低于基线值，平均值为67+/-13 μ M，对照实验中为725+/-65 μ M，P < 0.001。同时，总体葡萄糖产量减少了40%（5.5+/-11 vs. 9.3+/-0.7 gmol/kg/min，P < 0.001），丙氨酸的异生作用减少了近70%（0.32+/-0.09 vs. 1.00+/-0.18 mumol/kg/min，P < 0.001），而葡萄糖利用率增加了15%（10.8+/-1.4 vs. 9.3+/-0.7 mumol/kg/min）。我们的结论是，FFA发挥关键作用，在调解葡萄糖代谢的变化，在反调节，在这些条件下，FFA发挥更深刻的影响，对肝脏葡萄糖的生产比葡萄糖的利用。
In vitro studies indicate that FFA compete with glucose as an oxidative fuel in muscle and, in addition, stimulate gluconeogenesis in liver. During counterregulation of hypoglycemia, plasma FFA increase and this is associated with an increase in glucose production and a suppression of glucose utilization. To test the hypothesis that FFA mediate changes in glucose metabolism that occur during counterregulation, we examined the effects of acipimox, an inhibitor of lipolysis, on glucose production and utilization ([3-H-3]glucose), and incorporation of [U-C-14]-alanine into glucose during insulin-induced hypoglycemia. Eight normal volunteers were infused with insulin for 8 h to produce modest hypoglycemia (approximately 3 mM) on two occasions, first without acipimox (control) and then with acipimox administration (250 mg per os at 60 and 240 min). Despite identical plasma insulin concentrations, glucose had to be infused in the acipimox experiments (glucose-clamp technique) to maintain plasma glucose concentrations identical to those in control experiments. Acipimox completely prevented counterregulatory increases in lipolysis so that during the last 4 h plasma FFA were below baseline values and averaged 67+/-13 vs. 725+/-65 muM in control experiments, P < 0.001. Concomitantly, overall glucose production was reduced by 40% (5.5+/-11 vs. 9.3+/-0.7 gmol/kg per min, P < 0.001), and gluconeogenesis from alanine was reduced by nearly 70% (0.32+/-0.09 vs. 1.00+/-0.18 mumol/kg per min, P < 0.001), while glucose utilization increased by 15% (10.8+/-1.4 vs. 9.3+/-0.7 mumol/kg per min). We conclude that FFA play a critical role in mediating changes in glucose metabolism during counterregulation, and that under these conditions, FFA exert a much more profound effect on hepatic glucose production than on glucose utilization.