Hemorrhage induces the rapid development of hepatic insulin resistance (Retracted Article)
Hemorrhage induces the rapid development of hepatic insulin resistance (Retracted Article)
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DOI：
10.1152/ajpgi.00217.2002
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发表时间：
2003-01-01
影响因子：
4.5
通讯作者：
Messina, JL
中科院分区：
文献类型：
--
作者：
Ma, YC;Wang, P;Messina, JL
高血压是创伤和出血的早期代谢反应。肝脏胰岛素抵抗在这种高血糖症发展中的作用尚不清楚。本研究的目的是确定肝脏是否会出现胰岛素抵抗，并确定创伤和出血后可能受损的特定肝脏胰岛素信号通路。将雄性成年大鼠放血至40 mmHg的平均动脉压，并在该压力下维持90 min，然后用乳酸林格氏液复苏。数据显示，创伤和出血迅速诱导严重的高胰岛素血症，并伴有显著的高血糖，提示胰岛素抵抗的发展。创伤和出血后，肝脏胰岛素信号通过胰岛素诱导的磷脂酰肌醇3（PI 3）-激酶-Akt通路被取消，而ERK 1/2信号相对正常。肝脏、胰岛素和PI 3激酶依赖性基因IGF结合蛋白-1的调节（抑制）也丢失。目前的研究提供了令人信服的证据表明，在创伤和出血的联合作用下，肝脏胰岛素抵抗会迅速发生。
Hyperglycemia is an early metabolic response to trauma and hemorrhage. The role of hepatic insulin resistance to the development of this hyperglycemia is not well understood. The aim of this study was to determine whether the liver becomes insulin resistant and to identify the particular hepatic insulin signaling pathways that may be compromised following trauma and hemorrhage. Male adult rats were bled to a mean arterial pressure of 40 mmHg and maintained at that pressure for 90 min followed by resuscitation with Ringer lactate. Data showed that trauma and hemorrhage rapidly induced profound hyperinsulinemia in combination with significant hyperglycemia, suggesting the development of insulin resistance. After trauma and hemorrhage, hepatic insulin signaling via the insulin-induced phosphatidylinositol 3 (PI3)-kinase-Akt pathway was abolished, whereas ERK1/2 signaling was relatively normal. The regulation (inhibition) of a hepatic-, insulin-, and the PI3-kinase-dependent gene, IGF binding protein-1, was also lost. The present study provides convincing evidence of a rapid onset hepatic insulin resistance following a combination of trauma and hemorrhage.