Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-κB pathway in rat liver
Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-κB pathway in rat liver
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DOI：
10.2337/diabetes.54.12.3458
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发表时间：
2005-12-01
期刊：
影响因子：
7.7
通讯作者：
Ruderman, N
中科院分区：
文献类型：
--
作者：
Boden, G;She, PX;Ruderman, N
为了研究游离脂肪酸（FFAS）引起肝脏胰岛素抵抗的机制，我们在警觉的雄性大鼠中使用了正常血糖-高胰岛素钳夹，并输注了脂质/肝素（以升高或降低血浆FFAs）。FFA诱导的肝脏胰岛素抵抗与肝脏二酰甘油含量增加（+210%）、两种丝氨酸/苏氨酸激酶活性增加有关。（蛋白激酶C-δ和κ B [I κ B]激酶-β抑制剂），增加促炎性核因子-κ B的活化（NF-κ B）途径（I κ B激酶-β，+640%; I κ B-α，-54%;和NF-κ B，+73%），并增加炎性细胞因子的表达（肿瘤坏死因子-α，+1，700%和白细胞介素-1 β，+440%）和单核细胞趋化蛋白-1（+220%）的血浆水平。我们的结论是，脂肪酸引起肝脏胰岛素抵抗，这可能会产生过量的葡萄糖和高血糖症，并启动炎症过程中的肝脏，可能会导致脂肪性肝炎的发展。
To study mechanisms by which free fatty acids (FFAS) cause hepatic insulin resistance, we have used euglycemic-hyperinsulinemic clamping with And without infusion of lipid/heparin (to raise or to lower plasma FFAs) in alert male rats. FFA-induced hepatic insulin resistance was associated with increased hepatic diacylglycerol content (+210%), increased activities of two serine/threonine kinases (protein kinase C-delta and inhibitor of kappa B [I kappa B] kinase-beta), increased activation of the proinflammatory nuclear factor-kappa B (NF-kappa B) pathway (I kappa B kinase-beta, +640%; I kappa B-alpha, -54%; and NF-kappa B, +73%), and increased expression of inflammatory cytokines (tumor necrosis factor-alpha, +1,700% and interleukin-1 beta, +440%) and plasma levels of monocyte chemoattractant protein-1 (+220%). We conclude that FFAs caused hepatic insulin resistance, which can produce overproduction of glucose and hyperglycemia, and initiated inflammatory processes in the liver that could potentially result in the development of steatohepatitis.