Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-α, and FFAs to low-dose endotoxemia in humans
Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-α, and FFAs to low-dose endotoxemia in humans
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DOI：
10.1152/ajpendo.00468.2003
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发表时间：
2004-05-01
影响因子：
5.1
通讯作者：
Pedersen, BK
中科院分区：
文献类型：
--
作者：
Krogh-Madsen, R;Moller, K;Pedersen, BK
胰岛素治疗可提高危重患者的生存率。为了探索可能的作用机制，我们研究了在操纵血糖和胰岛素浓度期间内毒素对循环细胞因子、游离脂肪酸（FFA）和白细胞的影响。10名志愿者各接受了3项试验，在血糖正常期间（试验A，对照）、在15 mM高血糖钳夹期间（试验B）和在高胰岛素正常血糖钳夹期间（试验C）接受静脉推注内毒素（0.2 ng/kg）。内毒素诱导中性粒细胞计数增加、淋巴细胞计数减少以及TNF-α、IL-6和FFA血清水平升高。三项试验之间的TNF应答无差异;与试验A相比，试验B和C的晚期IL-6水平升高。试验A中内毒素诱导的FFA升高在试验B和C期间受到抑制。钳夹（试验B和Q）导致淋巴细胞计数减少，在内毒素注射后持续存在。我们的结论是，低剂量内毒素血症触发亚临床炎症反应和FFA升高。高胰岛素血清浓度诱导抗炎细胞因子IL-6更长时间增加并抑制FFA水平的发现表明，脓毒症患者的胰岛素治疗可能通过诱导抗炎和保护免受FFA毒性而发挥有益作用，从而抑制FFA诱导的胰岛素抵抗。
Insulin therapy to maintain euglycemia increases survival in critically ill patients. To explore possible mechanisms of action, we investigated the effect of endotoxin on circulating cytokines, free fatty acids (FFA), and leukocytes during manipulated plasma glucose and insulin concentrations. Ten volunteers underwent three trials each, receiving an intravenous bolus of endotoxin (0.2 ng/kg) during normoglycemia (trial A, control), during a hyperglycemic clamp at 15 mM (trial B), and during a hyperinsulinemic euglycemic clamp (trial C). Endotoxin induced an increase in neutrophil count, a decrease in lymphocyte count, and an increase in serum levels of TNF-alpha, IL-6, and FFA. There was no difference in the TNF response between the three trials; the IL-6 levels were increased during the late phase of trials B and C compared with trial A. The endotoxin-induced elevation in FFA in trial A was suppressed during trials B and C. Clamping (trials B and Q caused a reduction in lymphocyte count that persisted after endotoxin injection. We conclude that low-dose endotoxemia triggers a subclinical inflammatory response and an elevation in FFA. The finding that high insulin serum concentrations induce a more prolonged increase in the anti-inflammatory cytokine IL-6 and suppress the levels of FFA suggests that insulin treatment of patients with sepsis may exert beneficial effects by inducing anti-inflammation and protection against FFA toxicity, and thereby inhibit FFA-induced insulin resistance.