Insulin resistance and substrate utilization in human endotoxemia
Insulin resistance and substrate utilization in human endotoxemia
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DOI：
10.1210/jc.85.10.3770
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发表时间：
2000-10-01
影响因子：
5.8
通讯作者：
Carlson, GL
中科院分区：
文献类型：
--
作者：
Agwunobi, AO;Reid, C;Carlson, GL
感染导致胰岛素抵抗状态，但发病机制知之甚少。静脉注射细菌脂多糖（LPS）已被用于模拟感染引起的发热和全身炎症反应，但LPS是否诱导人胰岛素抵抗尚不清楚。为了研究LPS对胰岛素敏感性和底物利用的影响，我们在配对交叉研究中，健康志愿者（n = 6）在10小时正常血糖高胰岛素钳夹（胰岛素输注速率，80 mU/m2·min）开始后120分钟，接受20 U/kg大肠杆菌内毒素或生理盐水对照。LPS诱导发热、心动过速和轻度动脉低血压。LPS注射后120 min葡萄糖利用率突然增加（+64.1 +/-12.0%; P < 0.003），但随后逐渐下降，420 min时胰岛素抵抗明显（+1.9 +/-3.5%; P < 0.05）。葡萄糖利用率的降低与脓毒症中观察到的类似，与非氧化性葡萄糖处置受损相关，而与葡萄糖氧化异常无关。皮质醇和GH对LPS的反应具有足够的持续时间和幅度来解释胰岛素抵抗。LPS给药导致的代谢反应与脓毒症中观察到的代谢反应非常相似，可以为研究人类危重疾病中的胰岛素抵抗提供有用的模型。
Infection results in a state of insulin resistance, but the pathogenesis is poorly understood. Intravenous administration of bacterial lipopolysaccharide (LPS) has been used to mimic the febrile and systemic inflammatory responses to infection, but it is unclear whether LPS induces insulin resistance in man. To investigate the effects of LPS on insulin sensitivity and substrate utilization, we administered, in paired cross-over studies, either 20 U/kg Escherichia coli endotoxin or saline control to healthy volunteers (n = 6) 120 min after the start of a 10-h euglycemic hyperinsulinemic clamp (insulin infusion rate, 80 mU/m(2).min). LPS induced a fever, tachycardia, and mild arterial hypotension. Glucose utilization increased abruptly 120 min after LPS administration (+64.1 +/- 12.0%; P < 0.003), but then declined progressively, and insulin resistance was evident by 420 min (+1.9 +/- 3.5%; P < 0.05). The reduction in glucose utilization,like that observed in sepsis, was related to impaired nonoxidative glucose disposal and not abnormal glucose oxidation. The cortisol and GH responses to LPS were of sufficient duration and magnitude to explain the insulin resistance. LPS administration results in metabolic responses very similar to those observed in sepsis and could provide a useful model for the study of insulin resistance in human critical illness.